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1.
Ir Med J ; 115(1): 517, 2022 Jan 20.
Article in English | MEDLINE | ID: mdl-35279051

ABSTRACT

Aim Nutrition is the leading cause of chronic disease globally, yet it is unknown how much nutritional education GP trainees receive. The aim is to identify GP trainee attitudes to nutrition and compare with the programme directors who deliver this training. Methods A multicentre online survey questionnaire of 542 GP trainees in Ireland and 63 programme directors over 2 weeks in September 2019. ANOVA analysis was used to determine if there was an agreement between programme directors and trainees. Results 13 GP training schemes participated, with 93 trainees (16%) and 9 (14%) programme directors answering the survey. There was consensus and agreement between trainees and programme directors for the following; it is the role of the GP to promote a healthy diet; there are barriers to optimal nutritional management; there would be interest in further education. ANOVA analysis found that there was agreement from directors and trainees in the assertion that nutritional education to date is not adequate. Discussion There is an agreement between GP trainees and their programme directors that the nutritional educational component of GP training is an unmet need. This study highlights the need for an improvement in nutritional education to maximise the management of chronic disease in Irish general practice.


Subject(s)
General Practice , Attitude , Family Practice , Humans , Ireland , Surveys and Questionnaires
2.
Educ Prim Care ; 30(6): 375-380, 2019 11.
Article in English | MEDLINE | ID: mdl-31603388

ABSTRACT

We describe and evaluate the North Dublin City General Practitioner Training Programme (NDCGP), which was designed to educate doctors to work with the underserved. People who are marginalised have poorer health and less access to healthcare than the general population. Furthermore, these groups have significantly lower numbers of GPs per capita of population. Few GP training programmes are located in such communities, despite GPs tending to work in the areas where they trained. An evaluation of NDCGP training programme was conducted by sending a self-administered questionnaire to all graduates of the programme (2013-17). Thirty-seven graduates (88%) responded to the questionnaire. Thirty-six (97%) were either working as GPs in an area of deprivation or their work included services to a marginalised group. These 36 (97%) respondents indicated that continuing to serve deprived communities was in their long-term plans. The training provided trainees with the knowledge, understanding and a specific skill set to equip them to work with the underserved. Through teaching and exposure placements, trainees' confidence and empathy had increased and their prejudice and fear towards underserved patients had decreased. Conclusion: The NDCGP Training Programme achieved its aims. Replication of this model of education should be considered elsewhere.


Subject(s)
Education, Medical, Graduate/organization & administration , General Practitioners/education , Medically Underserved Area , Female , General Practice/education , General Practitioners/psychology , Humans , Ireland , Male , Self Care , Surveys and Questionnaires , Vulnerable Populations
3.
Ir J Med Sci ; 186(3): 541-546, 2017 Aug.
Article in English | MEDLINE | ID: mdl-27882501

ABSTRACT

BACKGROUND: Homeless people have excessively high morbidity and mortality rates, yet they face barriers accessing primary care. A mobile health clinic, staffed by GP registrars, was developed to provide services to homeless people, particularly rough sleepers and sex workers. AIM: The aims were to improve access to primary care and to challenge the stereotypes and prejudices of GP registrars through direct contact with homeless people. DESIGN AND SETTING: This was a qualitative study; questionnaires were completed on the mobile health clinic and two focus groups were conducted. METHODS: All service users were asked to complete a questionnaire over a 3 month period. Two focus groups were conducted with 6 and 14 GP registrars who had worked on the bus. RESULTS: There was an 80% response rate (116 of 145). Fifty-two percent had no Medical Card meaning that they had no way to access the free primary care to which they are entitled. Had the clinic not been available, over half would not have sought further treatment and 16% would have gone to an Emergency Department. Ninety-one percent of users rated the service 10/10. The focus groups found that GP registrars who worked on the mobile health clinic had decreased negative stereotypes, increased empathy, and more knowledge of homeless issues. Furthermore, they intended to ensure that homeless people will not face discrimination in their future practice. CONCLUSION: A GP Registrar-run Mobile Health Clinic achieved its aims of improving access to primary care for rough sleepers and sex workers, and challenging stereotypes of GP Registrars.


Subject(s)
Ambulatory Care Facilities/standards , Ill-Housed Persons/psychology , Telemedicine/standards , Female , Humans , Male , Prejudice , Qualitative Research
4.
Drug Alcohol Depend ; 154: 139-45, 2015 Sep 01.
Article in English | MEDLINE | ID: mdl-26188997

ABSTRACT

INTRODUCTION: Drug misuse has been identified as a significant problem in homeless populations. This study examines aspects of physical and mental health, perceived quality of life and health service use among homeless illicit drug users and compares these to non-drug users. METHODS: Participants were recruited through health clinics across Dublin. A questionnaire assessed participants' drug use, health and well-being, health behaviours and use of health services. Descriptive statistics are presented for the entire cohort and drug users separately. Logistic regression analysis was used to examine the relationship between drug use and (i) multimorbidity, (ii) anxiety and/or depression, (iii) perceived quality of life and (iv) use of health services. RESULTS: Of 105 participants recruited, 35 (33%) were current drug users. Current and previous drug users were significantly more likely to have multimorbidity than those who had never taken drugs (OR 4.86, 95% CI 1.00-23.66). There was no significant difference between drug users and non-drug users in the prevalence of anxiety and/or depression. Drug users were five times more likely than non-drug users to have a low perceived quality of life (OR 5.2, 95% CI 1.7-16.0). Health service utilization was high, although some services were used less by drug users (e.g., dentist and psychiatric outpatient services) while others were used more often (e.g., phoneline services and day care centres). CONCLUSION: This study highlights the high levels of drug use in this population and the negative impact of drug use on health and perceived quality of life of a homeless population in Dublin.


Subject(s)
Drug Users/psychology , Health Status , Ill-Housed Persons/psychology , Ill-Housed Persons/statistics & numerical data , Patient Acceptance of Health Care/statistics & numerical data , Quality of Life , Substance-Related Disorders/psychology , Adult , Drug Users/statistics & numerical data , Female , Humans , Ireland/epidemiology , Male , Substance-Related Disorders/epidemiology , Surveys and Questionnaires , Young Adult
5.
J Endocrinol ; 216(1): 99-109, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23086141

ABSTRACT

The neuropeptide apelin is expressed in hypothalamic paraventricular and supraoptic nuclei and mediates its effects via activation of the apelin receptor (APJ). Evidence suggests a role for apelin and APJ in mediating the neuroendocrine response to stress. To understand the physiological role of APJ in regulation of the hypothalamic-pituitary-adrenal (HPA) axis, we measured ACTH and corticosterone (CORT) plasma levels in male and female mice lacking APJ (APJ knockout, APJ KO) and in wild-type controls, in response to a variety of acute stressors. Exposure to mild restraint, systemic injection of lipopolysaccharide (LPS), insulin-induced hypoglycaemia and forced swim (FS) stressors, elevated plasma ACTH and CORT levels in wild-type mice. Acute mild restraint significantly increased plasma ACTH and CORT to a similar level in APJ KO mice as in wild-type mice. However, an intact APJ was required for a conventional ACTH, but not CORT, response to LPS administration in male mice and to insulin-induced hypoglycaemia in male and female mice. In contrast, APJ KO mice displayed an impaired CORT response to acute FS stress, regardless of gender. These data indicate that APJ has a role in regulation of the HPA axis response to some acute stressors and has a gender-specific function in peripheral immune activation of the HPA axis.


Subject(s)
Hypothalamo-Hypophyseal System/metabolism , Neuroendocrine Cells/metabolism , Pituitary-Adrenal System/metabolism , Receptors, G-Protein-Coupled/metabolism , Stress, Physiological , Stress, Psychological/metabolism , Adrenocorticotropic Hormone/blood , Adrenocorticotropic Hormone/metabolism , Animals , Apelin Receptors , Circadian Rhythm , Corticosterone/blood , Corticosterone/metabolism , Crosses, Genetic , Disease Models, Animal , Female , Hypothalamo-Hypophyseal System/immunology , Hypothalamo-Hypophyseal System/pathology , In Situ Hybridization , Male , Mice , Mice, Knockout , Mutant Proteins/metabolism , Neuroendocrine Cells/immunology , Neuroendocrine Cells/pathology , Pituitary-Adrenal System/immunology , Pituitary-Adrenal System/pathology , Receptors, G-Protein-Coupled/genetics , Sex Characteristics , Stress, Psychological/blood , Stress, Psychological/immunology
6.
Ir J Med Sci ; 181(1): 43-8, 2012 Mar.
Article in English | MEDLINE | ID: mdl-21850472

ABSTRACT

BACKGROUND: The methadone protocol placed responsibility on general practitioners (GPs) for the methadone treatment of stabilised drug-addicted patients. The protocol emphasised a medico-pharmacological model with minor reference to psychotherapeutic treatment. AIM: This qualitative study investigated how primary care GPs in Ireland use psychotherapeutic interventions in the treatment of methadone patients. METHOD: A grounded theory methodology was used. FINDINGS: There is a wide variation in the beliefs and knowledge of methadone-prescribing GPs regarding the efficacy of psychotherapeutic interventions for patients on methadone maintenance. GPs do not formally integrate psychotherapeutic interventions into methadone patient treatment. Accessing psychotherapeutic services raises concerns for GPs in terms of availability, location and quality. Primary care GPs who offer methadone maintenance view opiate abuse as a health issue similar to other such issues within their community. They take a holistic view of their methadone patient and, without formal guidelines, develop individual approaches to the use of psychotherapeutic interventions. The absence of a framework for the use of psychotherapeutic interventions in primary care methadone treatment in Ireland militates against the development of a basis for improving practice.


Subject(s)
General Practice , Opioid-Related Disorders/therapy , Practice Patterns, Physicians' , Primary Health Care , Psychotherapy , Attitude of Health Personnel , Directive Counseling , Humans , Ireland , Methadone/therapeutic use , Narcotics/therapeutic use , Opiate Substitution Treatment , Referral and Consultation
7.
Ir J Med Sci ; 180(2): 475-8, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21290198

ABSTRACT

INTRODUCTION: There have been reports of thalidomide-affected people suffering a deterioration in their disability over time [1, 2]. This study assessed changes in disabilities among thalidomide-affected people in the Irish population. METHODS: A questionnaire, assessing musculo-skeletal health, quality-of-life, general health and illness intrusiveness was sent to 26 people affected by thalidomide in the Republic of Ireland. RESULTS: Seventeen (65%) responded. Six (35%) respondents were not working as a result of their disability. Eleven (65%) reported a worsening of their disability over time, with nine of them reporting the deterioration as moderate to severe. The impact of this decline was measured by respondents in terms of ability to perform daily tasks, emotional health and finances (due to extra costs related to clothing, transport, housing alterations and heating). CONCLUSION: There is a need to continually review the physical, psychological and social needs of thalidomide survivors in order to ensure optimum care is made available.


Subject(s)
Disabled Persons/psychology , Health Status , Musculoskeletal Diseases/congenital , Prenatal Exposure Delayed Effects , Quality of Life/psychology , Thalidomide/adverse effects , Activities of Daily Living , Adult , Arm/abnormalities , Female , Humans , Leg/abnormalities , Male , Middle Aged , Mobility Limitation , Musculoskeletal Diseases/psychology , Pain , Pregnancy
8.
J Neuroendocrinol ; 23(1): 12-9, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20874763

ABSTRACT

Vasopressin V1b receptor knockout (V1b⁻/⁻) mice were used to investigate a putative role for the V1b receptor (V1bR) in fluid regulation and in the hypothalamic-neurohypophysial system (HNS) and hypothalamic-pituitary-adrenal (HPA) axis responses to osmotic stress induced by water deprivation (WD). Male wild-type and V1b⁻/⁻ mice were housed in metabolic cages to allow determination of water intake and urine volume and osmolality. When provided with food and water ad lib., spontaneous urine volume and urine osmolality did not differ between genotypes. Similarly, WD for 24 h caused comparable decreases in urine volume and increases in urine osmolality irrespective of genotype. WD resulted in an increase in plasma corticosterone concentration in wild-type animals; however, this WD-induced increase in plasma corticosterone was significantly attenuated in V1b⁻/⁻ mice. Comparable increases in neuronal activation, indicated by increased c-fos mRNA expression, and in vasopressin mRNA expression occurred in both the supraoptic nucleus and paraventricular nucleus (PVN) of wild-type and V1b⁻/⁻ mice following WD; however, the WD-induced decrease in corticotrophin-releasing hormone mRNA expression seen in the PVN of wild-type mice was not observed in the PVN of V1b⁻/⁻ mice. These data suggest that, although the vasopressin V1bR is not required for normal HNS function, it is necessary for a full HPA-axis response to the osmotic stress of WD.


Subject(s)
Corticosterone/blood , Dehydration , Receptors, Vasopressin/physiology , Stress, Physiological , Adrenocorticotropic Hormone/blood , Animals , In Situ Hybridization , Male , Mice , Mice, Knockout , Receptors, Vasopressin/genetics
9.
Stress ; 14(1): 98-115, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20828336

ABSTRACT

The distribution, pharmacology and function of the arginine vasopressin (Avp) 1b receptor subtype (Avpr1b) has proved more challenging to investigate compared to other members of the Avp receptor family. Avp is increasingly recognised as an important modulator of the hypothalamic-pituitary-adrenal (HPA) axis, an action mediated by the Avpr1b present on anterior pituitary corticotrophs. The Avpr1b is also expressed in some peripheral tissues including pancreas and adrenal, and in the hippocampus (HIP), paraventricular nucleus and olfactory bulb of the rodent brain where its function is unknown. The central distribution of Avpr1bs is far more restricted than that of the Avpr1a, the main Avp receptor subtype found in the brain. Whether Avpr1b expression in rodent tissues is dependent on differences in the length of microsatellite dinucleotide repeats present in the 5' promoter region of the Avpr1b gene remains to be determined. One difficulty of functional studies on the Avpr1b, especially its involvement in the HPA axis response to stress, which prompted the generation of Avpr1b knockout (KO) mouse models, was the shortage of commercially available Avpr1b ligands, particularly antagonists. Research on mice lacking functional Avpr1bs has highlighted behavioural deficits in social memory and aggression. The Avpr1b KO also appears to be an excellent model to study the contribution of the Avpr1b in the HPA axis response to acute and perhaps some chronic (repeated) stressors where corticotrophin-releasing hormone and other genes involved in the HPA axis response to stress do not appear to compensate for the loss of the Avpr1b.


Subject(s)
Receptors, Vasopressin/physiology , Stress, Physiological/physiology , Aggression , Animals , Brain/metabolism , Hypothalamo-Hypophyseal System/physiopathology , Mice , Mice, Knockout , Pituitary-Adrenal System/physiopathology , Receptors, Vasopressin/genetics , Tissue Distribution
10.
J Neuroendocrinol ; 22(11): 1173-80, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20846299

ABSTRACT

Arginine vasopressin (AVP) synthesised in the parvocellular region of the hypothalamic paraventricular nucleus and released into the pituitary portal vessels acts on the 1b receptor subtype (Avpr1b) present in anterior pituitary corticotrophs to modulate the release of adrenocorticotrophic hormone (ACTH). Corticotrophin-releasing hormone is considered the major drive behind ACTH release; however, its action is augmented synergistically by AVP. To determine the extent of vasopressinergic influence in the hypothalamic-pituitary-adrenal axis response to restraint and forced swimming stress, we compared the stress hormone levels [plasma ACTH in both stressors and corticosterone (CORT) in restraint stress only] following acute stress in mutant Avpr1b knockout (KO) mice compared to their wild-type controls following the administration of a novel Avpr1b antagonist. Restraint and forced swimming stress-induced increases in plasma ACTH were significantly diminished in mice lacking a functional Avpr1b and in wild-type mice that had been pre-treated with Avpr1b antagonist. A corresponding decrease in plasma CORT levels was also observed in acute restraint-stressed knockout male mice, and in Avpr1b-antagonist-treated male wild-type mice. By contrast, plasma CORT levels were not reduced in acutely restraint-stressed female knockout animals, or in female wild-type animals pre-treated with Avpr1b antagonist. These results demonstrate that pharmacological antagonism or inactivation of Avpr1b causes a reduction in the hypothalamic-pituitary-adrenal (HPA) axis response, particularly ACTH, to acute restraint and forced swimming stress, and show that Avpr1b knockout mice constitute a model by which to study the contribution of Avpr1b to the HPA axis response to acute stressors.


Subject(s)
Receptors, Vasopressin/genetics , Receptors, Vasopressin/physiology , Stress, Psychological/genetics , Stress, Psychological/prevention & control , Swimming/psychology , Adrenocorticotropic Hormone/blood , Animals , Antidiuretic Hormone Receptor Antagonists , Handling, Psychological , Hydrocortisone/blood , Hypothalamo-Hypophyseal System/drug effects , Hypothalamo-Hypophyseal System/physiology , Mice , Mice, Inbred C57BL , Mice, Knockout , Pituitary-Adrenal System/drug effects , Pituitary-Adrenal System/physiology , Restraint, Physical
11.
J Neuroendocrinol ; 22(4): 301-8, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20136689

ABSTRACT

The expression of the novel peptide apelin and its receptor APJ within specific regions of the brain, in particular the magnocellular neurones of the hypothalamus and the circumventricular organs, has implicated the apelinergic system in mechanisms controlling fluid homeostasis. In addition, apelin and APJ are considered to be involved in controlling arginine vasopressin (AVP) secretion into the circulation and release within the hypothalamic-neurohypophysial system. To clarify the role of APJ during regulation of fluid homeostasis, we compared the effects of osmotic stimulation on the urinary concentrating capacities and central nervous system responses of salt-loaded (SL) and water-deprived (WD) female APJ knockout (APJ(-/-)) mice and wild-type controls. SL resulted in a significantly increased urine volume in APJ(-/-) mice compared to wild-type controls, whereas WD in APJ(-/-) mice failed to reduce urine volume as seen in wild-type controls. AVP transcripts in the supraoptic and paraventricular nuclei and plasma AVP concentrations were significantly attenuated in SL APJ(-/-) mice compared to SL wild-type, but increased comparably in wild-type and APJ(-/-) mice after WD. Analysis of c-fos mRNA expression in the median preoptic nucleus and subfornical organ in response to either WD or SL showed attenuated expression in APJ(-/-) compared to wild-type mice. These findings further implicate the apelinergic system in mechanisms controlling fluid homeostasis, particularly at a neuroendocrine level, and suggest stimulus-specific involvement in vasopressinergic activity.


Subject(s)
Neurosecretory Systems/physiology , Receptors, G-Protein-Coupled/genetics , Animals , Apelin Receptors , Body Fluids/metabolism , Body Fluids/physiology , Female , Gene Expression Regulation , Homeostasis/physiology , Mice , Mice, Inbred C57BL , Mice, Knockout , Neurosecretory Systems/metabolism , Osmotic Pressure/physiology , Physical Stimulation , Receptors, G-Protein-Coupled/physiology , Salts/pharmacology , Stress, Physiological/physiology , Vasopressins/metabolism , Water Deprivation/physiology , Water-Electrolyte Imbalance/blood , Water-Electrolyte Imbalance/physiopathology , Water-Electrolyte Imbalance/urine
12.
Ir Med J ; 101(1): 10-2, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18369016

ABSTRACT

In 2001 the frequency of reviewing medical-card eligibility was increased. This study assessed the impact of this policy change on patient entitlement to free health care. Data on reasons for patient removal from a GP's General Medical Services (GMS) list during a two and a half year period was analysed. During this period, 1489 (89% CI 87-91%) patients from the practice list were removed for non-return of review forms. Forty patients randomly selected from patients deleted from the list in 2006 were interviewed. Sixty percent said they had not received a review form and 91% (CI 82-100%) believed they were entitled to a medical card. In the period without medical card cover, cost prevented 11% (CI 1-21%) of those who felt they were eligible from accessing medical care while 26% (CI 12-40%) paid 'out-of-pocket'. This study shows that a bureaucratic policy change has negatively affected access to health care.


Subject(s)
Delivery of Health Care , Eligibility Determination/statistics & numerical data , Forms and Records Control , Health Services Accessibility , Health Services Needs and Demand/statistics & numerical data , Medical Assistance/statistics & numerical data , Adolescent , Adult , Aged , Cross-Sectional Studies , Female , Health Services Needs and Demand/economics , Humans , Income , Ireland/epidemiology , Male , Medical Assistance/economics , Middle Aged , Physicians, Family/statistics & numerical data , Retrospective Studies
13.
J Neuroendocrinol ; 20(5): 597-605, 2008 May.
Article in English | MEDLINE | ID: mdl-18363802

ABSTRACT

Arginine vasopressin and corticotrophin-releasing hormone synthesised and released from the hypothalamic paraventricular nucleus are the prime mediators of the hypothalamic-pituitary-adrenal (HPA) axis response to stress. These neurohormones act synergistically to stimulate adrenocorticotophin (ACTH) secretion from the anterior pituitary, culminating in an increase in circulating glucocorticoids. Arginine vasopressin mediates this action at the arginine vasopressin 1b receptor (Avpr1b) located on pituitary corticotrophs. Arginine vasopressin is regarded as a minor ACTH secretagogue in rodents but evidence suggests that it has a role in mediating the neuroendocrine response to some acute and chronic stressors. To investigate the role of the Avpr1b in the HPA axis response to an acute and chronic (repeated) stress, we measured the plasma ACTH and corticosterone concentrations in three stress paradigms in both Avpr1b knockout and wild-type mice. Single acute exposure to restraint, forced swim and change in environment stressors elevated both plasma ACTH and corticosterone concentrations in wild-type animals. Conversely, the ACTH response to the acute stressors was significantly attenuated in Avpr1b knockout mice compared to their wild-type counterparts. Plasma corticosterone concentrations were reduced in Avpr1b knockout mice in response to change in environment but not to mild restraint or forced swim stress. Irrespective of genotype, there was no difference in the plasma ACTH or corticosterone concentrations in response to acute and repeated stressors. The data show that a functional Avpr1b is required for an intact pituitary ACTH response to the acute and chronic stressors used in this study. Furthermore, the normal corticosterone response to repeated exposure to change in environment stress also requires the Avpr1b to drive HPA axis responsiveness.


Subject(s)
Pituitary-Adrenal System/physiology , Receptors, Vasopressin/genetics , Restraint, Physical , Social Environment , Stress, Psychological/genetics , Swimming , Adaptation, Psychological/physiology , Adrenocorticotropic Hormone/blood , Animals , Corticosterone/blood , Hypothalamo-Hypophyseal System/physiology , Male , Mice , Mice, Knockout , Periodicity , Stress, Psychological/physiopathology , Time Factors
14.
J Neuroendocrinol ; 19(7): 543-51, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17561882

ABSTRACT

The arginine vasopressin (Avp) 1b receptor (Avpr1b) present on anterior pituitary corticotrophs is involved in the stimulation of adrenocorticotrophic hormone (ACTH) secretion, especially during times of stress. Corticotrophin-releasing hormone (CRH) is considered the major ACTH secretagogue during acute stress whereas Avp appears to be the more dominant mediator of the hypothalamic-pituitary-adrenal (HPA) axis response during chronic stress situations. To investigate the role of the Avpr1b in the HPA axis response to acute stress, we measured ACTH and corticosterone (CORT) plasma levels in Avpr1b knockout (KO) mice and wild-type controls in response to bacterial lipopolysaccharide (LPS) challenge and ethanol (EtOH) administration. Mice deficient in Avpr1b had markedly compromised plasma ACTH and CORT responses to acute (30 min) LPS, but normal ACTH and CORT response to more extended exposure (4 h) to the immune system activator. The plasma ACTH and CORT levels stimulated by intoxicating, sedative doses of EtOH (3.2 and 4 g/kg) were significantly decreased in the Avpr1b KO mice compared to wild-type littermates. Significantly higher EtOH-induced plasma ACTH and CORT secretion was measured in female than in male Avpr1b wild-type mice. There were no differences in the blood alcohol levels following acute EtOH administration in Avpr1b KO or wild-type mice of either gender. Our results clearly suggest that Avpr1b plays a significant role in the HPA axis response to acute immune stress and EtOH intoxication.


Subject(s)
Ethanol/pharmacology , Lipopolysaccharides/pharmacology , Receptors, Vasopressin/physiology , Stress, Physiological/physiopathology , Adrenal Glands/drug effects , Animals , Ethanol/blood , Female , Hypothalamo-Hypophyseal System/drug effects , Male , Mice , Mice, Knockout , Receptors, Vasopressin/metabolism
15.
J Neuroendocrinol ; 15(11): 1095-101, 2003 Nov.
Article in English | MEDLINE | ID: mdl-14622440

ABSTRACT

The apelin receptor (APJ receptor, APJR) has recently come to prominence following the isolation and identification of its endogenous ligand, apelin, from bovine stomach tissue extracts. Investigation of APJR mRNA expression has revealed a hypothalamic distribution similar to that of vasopressin suggesting that the apelin-APJR system may be involved in the regulation of the hypothalamic-adrenal-pituitary (HPA) stress axis. To investigate whether APJR is involved in the regulation of hypothalamic function during stress, APJR mRNA expression levels were measured by in situ hybridization in the hypothalamus of rats subjected to acute and repeated restraint stress. Acute stress caused an increase in APJR mRNA expression in the hypothalamic parvocellular paraventricular nucleus (pPVN) while repeated restraint stress induced a sustained up-regulation of pPVN APJR mRNA expression in intact rats. Removal of endogenous glucocorticoids by adrenalectomy also resulted in an increased expression of APJR mRNA in the PVN, suggesting a negative regulation of APJR mRNA expression by glucocorticoids. The role of glucocorticoids in mediating these stress-induced changes was investigated by analysing the effects of acute and repeated restraint stress on APJR mRNA levels in adrenalectomized rats. In these rats, APJR mRNA expression levels did not change above the already elevated levels of adrenalectomized-control rats. These data suggest that acute and repeated stress exert a stimulatory influence on APJR mRNA expression at the hypothalamic level that may be dependent on basal levels of circulating glucocorticoids, and further suggest a role for APJR in the regulation of hypothalamic function.


Subject(s)
Glucocorticoids/physiology , Paraventricular Hypothalamic Nucleus/metabolism , Receptors, G-Protein-Coupled/genetics , Stress, Physiological/metabolism , Adrenal Glands/metabolism , Adrenalectomy , Animals , Apelin , Apelin Receptors , Carrier Proteins/metabolism , Corticosterone/blood , In Situ Hybridization , Intercellular Signaling Peptides and Proteins , Male , RNA, Messenger/analysis , Rats , Rats, Wistar , Receptors, G-Protein-Coupled/metabolism , Restraint, Physical , Up-Regulation
16.
J Neuroendocrinol ; 15(7): 661-6, 2003 Jul.
Article in English | MEDLINE | ID: mdl-12787050

ABSTRACT

The novel apelin receptor (APJ receptor, APJR) has a restricted expression in the central nervous system suggestive of an involvement in the regulation of body fluid homeostasis. The endogenous ligand for APJR, apelin, is also highly concentrated in regions that are involved in the control of drinking behaviour. While the physiological roles of APJR and apelin are not fully known, apelin has been shown to stimulate drinking behaviour in rats and to have a regulatory effect on vasopressin release from magnocellular neurones of the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. To determine the role of APJR in the regulation of water balance, this study examined the effects of osmotic stimulation on the expression of APJR mRNA in the magnocellular PVN (mPVN) and SON of salt-loaded and water-deprived rats. Intake of 2% NaCl and water deprivation for 48 h induced expression of APJR mRNA in the mPVN and SON. Using dual-label in situ hybridization histochemistry, we also investigated whether APJR is colocalized within vasopressin neurones in control, salt-loaded and water-deprived rats. APJR mRNA was found to colocalize with a small population of vasopressin-containing magnocellular neurones in control and water-deprived rats. Salt-loading resulted in an increased colocalization of APJR and vasopressin mRNAs in the SON. These data verify a role for APJ receptors in body fluid regulation and suggest a role for apelin in the regulation of vasopressin-containing neurones via a local autocrine/paracrine action of the peptide.


Subject(s)
Carrier Proteins/physiology , Gene Expression , Neurons/chemistry , Paraventricular Hypothalamic Nucleus/chemistry , Receptors, Dopamine D2/genetics , Receptors, G-Protein-Coupled , Sodium Chloride/administration & dosage , Supraoptic Nucleus/chemistry , Animals , Apelin , Apelin Receptors , Gene Expression/drug effects , In Situ Hybridization , In Vitro Techniques , Intercellular Signaling Peptides and Proteins , Male , RNA, Messenger/analysis , Rats , Rats, Wistar , Receptors, Dopamine D2/physiology , Vasopressins/genetics , Water Deprivation , Water-Electrolyte Balance
17.
Mol Psychiatry ; 7(9): 975-84, 2002.
Article in English | MEDLINE | ID: mdl-12399951

ABSTRACT

Increased aggression is commonly associated with many neurological and psychiatric disorders. Current treatments are largely empirical and are often accompanied by severe side effects, underscoring the need for a better understanding of the neural bases of aggression. Vasopressin, acting through its 1a receptor subtype, is known to affect aggressive behaviors. The vasopressin 1b receptor (V1bR) is also expressed in the brain, but has received much less attention due to a lack of specific drugs. Here we report that mice without the V1bR exhibit markedly reduced aggression and modestly impaired social recognition. By contrast, they perform normally in all the other behaviors that we have examined, such as sexual behavior, suggesting that reduced aggression and social memory are not simply the result of a global deficit in sensorimotor function or motivation. Fos-mapping within chemosensory responsive regions suggests that the behavioral deficits in V1bR knockout mice are not due to defects in detection and transmission of chemosensory signals to the brain. We suggest that V1bR antagonists could prove useful for treating aggressive behavior seen, for example, in dementias and traumatic brain injuries.


Subject(s)
Aggression/physiology , Behavior, Animal/physiology , Brain Chemistry/genetics , Receptors, Vasopressin/genetics , Age Factors , Animals , Body Temperature/physiology , Corticosterone/blood , Eating/physiology , Exploratory Behavior/physiology , Female , Male , Maze Learning/physiology , Mice , Mice, Inbred C57BL , Mice, Knockout , Motor Activity/physiology , Neurons/chemistry , Phenotype , Proto-Oncogene Proteins c-fos/analysis , Recognition, Psychology/physiology , Sexual Behavior, Animal/physiology , Stress, Physiological/physiopathology , Testosterone/blood , Visual Perception/physiology
18.
Biochim Biophys Acta ; 1492(1): 72-80, 2000 Jun 21.
Article in English | MEDLINE | ID: mdl-11004481

ABSTRACT

The human APJ receptor is a G protein-coupled receptor which functions as an efficient alternative co-receptor for a number of human immunodeficiency virus type 1 and simian immunodeficiency virus strains. We have cloned the rat APJ receptor, which we term B78/apj, and have mapped the mRNA distribution of both the receptor and its natural ligand apelin in rat tissues. Northern blot analysis showed a similar pattern of expression for B78/apj and apelin mRNAs with hybridising transcripts seen in the lung, heart, skeletal muscle, kidney, brain and liver. In situ hybridisation histochemistry studies revealed intense B78/apj gene expression in the parenchyma of the lung, a sub-population of glomeruli in the kidney, the corpora lutea of the ovary and isolated cells of the anterior lobe of the pituitary. B78/apj mRNA had a striking and unique distribution within the central nervous system (CNS) where receptor expression was found in cells within the meninges around the brain, in the posterior magnocellular and medial parvocellular areas of the hypothalamic paraventricular nucleus and in the supraoptic nucleus. This hypothalamic distribution offers a possible specific role of this receptor in mediating neuroendocrine responses in the CNS.


Subject(s)
Brain/metabolism , Carrier Proteins/metabolism , Receptors, Dopamine D2/genetics , Receptors, G-Protein-Coupled , Amino Acid Sequence , Animals , Apelin , Apelin Receptors , Base Sequence , Blotting, Northern , Brain/cytology , Cloning, Molecular , DNA, Complementary/analysis , Humans , Immunohistochemistry , In Situ Hybridization , Intercellular Signaling Peptides and Proteins , Ligands , Molecular Sequence Data , RNA, Messenger/metabolism , Rats , Rats, Wistar , Receptors, Dopamine D2/metabolism , Sequence Analysis, DNA , Sequence Homology, Amino Acid , Tissue Distribution
19.
Endocrinology ; 139(1): 350-7, 1998 Jan.
Article in English | MEDLINE | ID: mdl-9421433

ABSTRACT

Somatostatin (SRIF) exerts multiple inhibitory actions throughout the body by binding to specific SRIF receptors (sst). In recent years, five subtypes of SRIF receptors (sst1-5) have been cloned. In this study, 35S-labeled complementary RNA probes were used for in situ hybridization to localize the sst1-5 messenger RNAs (mRNAs) in the rat testis and examine the changes in their distribution during the cycle of the seminiferous epithelium. We found that sst 1-3 mRNAs were visualized in rat testes and were mainly localized within the seminiferous tubules. The signal for sst3 mRNA was also found in interstitial cells. sst4 and 5 mRNAs were not detected in rat testes with the method used in this study. In Sertoli cells, the most intense labeling for sst1 and 3 mRNAs was in stages IV-VII of the cycle of the seminiferous epithelium, which coincided with the lowest labeling intensity for sst2. In germ cells, sst1-3 mRNAs showed similar patterns of distribution. In these cells, sst1-3 mRNA was not observed at the early steps of spermatogenesis. Positive signals for sst1-3 mRNAs were first apparent in the pachytene spermatocytes at stage VII and last until stage XII and in the diplotene spermatocyte at stage XIII. Positive signals for sst1-3 were also detected in round spermatids at stages I-VIII. Labeling of spermatids dramatically decreased at stage IX, when these cells began their elongating changes. The presence of three sst in testis suggests that SRIF may play an essential role in testicular function.


Subject(s)
RNA, Messenger/analysis , Receptors, Somatostatin/genetics , Testis/metabolism , Animals , Base Sequence , Male , Molecular Sequence Data , Rats , Rats, Sprague-Dawley , Seminiferous Epithelium/metabolism
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