Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 47
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Can J Surg ; 44(1): 25-32, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11220795

RESUMO

OBJECTIVE: To develop a collaborative approach for the treatment of gastrointestinal carcinoid tumours and carcinoid syndrome. PARTICIPANTS: Leaders in the medical, endocrine, radiologic and surgical treatment of carcinoid disease were selected to present papers at the Carcinoid Syndrome Symposium on Treatment Modalities for Gastrointestinal Carcinoid Tumours and participate in the workshop that followed. EVIDENCE: A multidisciplinary symposium with experts in the field of carcinoid syndrome was organized at the University of Calgary. Data presented, participation of the attendees and a review of the literature were used in the workshop to develop a collaborative approach to the management of carcinoid tumours. BENEFITS: Carcinoid tumours are rare and few centres have large experiences in their treatment. Before the development of this collaboration, patients with carcinoid tumours received a unidisciplinary approach depending on referral patterns. The development of a multidisciplinary neuroendocrine clinic helped to unify the approach to these patients, yet a consensus on the treatment of carcinoid tumours was lacking. The expertise at the symposium allowed for consensus and the development of treatment algorithms, including biochemical screening, radiographic localization and surgical intervention, for gastrointestinal carcinoid tumours. The role of medical and hormonal therapy after cytoreducion is presented. RECOMMENDATION: Patients with carcinoid tumours require a multidisciplinary approach to their care.


Assuntos
Tumor Carcinoide/terapia , Neoplasias Gastrointestinais/terapia , Algoritmos , Neoplasias do Apêndice/diagnóstico por imagem , Tumor Carcinoide/diagnóstico por imagem , Tumor Carcinoide/secundário , Neoplasias Gastrointestinais/diagnóstico por imagem , Neoplasias Gastrointestinais/secundário , Humanos , Ácido Hidroxi-Indolacético/urina , Neoplasias Hepáticas/secundário , Síndrome , Tomografia Computadorizada por Raios X
2.
Clin Invest Med ; 23(3): 172-87, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10911548

RESUMO

Acromegaly is a chronic, debilitating condition caused by excessive secretion of growth hormone (GH). In the majority of cases the condition results from benign pituitary adenomas or, rarely, from ectopic production of GH-releasing hormone. Regardless of the cause, excess GH results in physical disfigurement associated with arthropathy, diabetes, hypertension, cardiac dysfunction, obstructive sleep apnea and colonic neoplasia. The death rate for acromegalic patients is 2 to 3 times higher than that of the general population, but with appropriate reduction of GH hypersecretion it tends to shift into the normal range. Treatment is thus aimed at normalizing GH secretion; eradicating or stabilizing the pituitary tumour while preserving normal pituitary function, and managing the associated complications. The treatment modalities available to achieve these objectives include transsphenoidal surgery, pharmacotherapy and radiation, or various combinations of these. This review provides an update on our current understanding of the pathophysiology of GH hypersecretion in acromegaly, the newly defined diagnostic criteria and the end point for a cure for acromegaly, and on new developments in drug treatment with the advent of slow-release forms of somatostatin analogues and the longer-acting dopamine receptor agonists, as well as in the area of radiotherapy. Its main purpose is to guide any physician involved in the diagnosis and management of patients with acromegaly.


Assuntos
Acromegalia/diagnóstico , Acromegalia/terapia , Guias de Prática Clínica como Assunto , Acromegalia/mortalidade , Acromegalia/cirurgia , Canadá , Custos de Cuidados de Saúde , Hormônio do Crescimento Humano/antagonistas & inibidores , Hormônio do Crescimento Humano/metabolismo , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Hipófise/metabolismo , Hipófise/patologia , Hipófise/fisiopatologia , Hipófise/efeitos da radiação , Radioterapia , Receptores da Somatotropina/antagonistas & inibidores , Receptores da Somatotropina/metabolismo , Somatostatina/análogos & derivados , Somatostatina/farmacologia , Somatostatina/uso terapêutico
3.
Diabetes Care ; 21(3): 444-50, 1998 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9540030

RESUMO

Recent research on development of the implantable artificial pancreas for treatment of diabetes is reviewed, based on a Medline literature search that focused on glucose sensors, insulin pumps, and pump control systems. To achieve a closed feedback loop, a clinically applicable implantable artificial pancreas requires miniaturization and coordination of three components: an insulin pump, a blood glucose monitor, and a control system. Recent clinical studies have demonstrated that implantable insulin pumps are feasible for satisfactory control of diabetes for over a year, with the major complication being obstruction of the infusion catheter. Research on continuous glucose sensors has predominantly used the glucose-oxidase reaction or near-infrared light spectroscopy. Implantable glucose oxidase sensors have been limited by local factors causing unstable signal output, whereas optical sensors must overcome interference by substances with absorption spectra similar to glucose. Investigators have developed control algorithms in an effort to stabilize operation of the integrated artificial pancreas in the face of variations in sensor output and pump function. The ultimate goals of fully automatic glucose control by an artificial pancreas include prevention or delay of chronic complications of diabetes, lowered risk of hypoglycemia, and less patient inconvenience and discomfort than with multiple daily glucose self-tests and insulin injection. The recent developments of optical glucose sensing, radiotelemetry systems to link pump and sensor, and miniaturization and refinement of insulin pumps are significant steps toward a clinically applicable artificial pancreas.


Assuntos
Diabetes Mellitus/tratamento farmacológico , Sistemas de Infusão de Insulina/tendências , Técnicas Biossensoriais , Glicemia/metabolismo , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Bombas de Infusão Implantáveis , Insulina/administração & dosagem , Insulina/uso terapêutico , Telemetria/instrumentação
4.
Clin Invest Med ; 19(4): 259-70, 1996 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8853574

RESUMO

OBJECTIVE: To reach a Canadian consensus on the diagnosis and management of acromegaly. DIAGNOSIS: documenting autonomous growth-hormone hypersecretion and imaging of the pituitary. TREATMENT: surgical resection, adjunctive therapy with bromocriptine or octreotide and radiation therapy. OUTCOMES: Reduction of the morbidity and mortality associated with acromegaly. EVIDENCE: Review of international literature. VALUES: Achievement of consensus among a panel of Canadian endocrinologists. BENEFITS, HARMS AND COSTS: Acromegaly is a chronic debilitating condition that is associated with morbidity and mortality. This consensus statement is designed to improve the diagnosis and management of this rare condition in order to minimize the negative outcomes. Costs were not considered. RECOMMENDATIONS: The diagnosis of acromegaly is established by documenting autonomous growth-hormone hypersecretion and by imaging the pituitary. Surgical resection is the cornerstone of treatment; however, adjunctive therapy is often needed. Although growth-hormone reduction is often associated with alleviation of symptoms, an attempt should also be made to normalize levels of growth hormone and its target growth factor, insulin-like growth factor-I (IGF-I). Persistent secretion of excess growth hormone and IGF-I may pose significant long-term health risks. A suggested therapeutic algorithm is provided. The ease of administration of bromocriptine should prompt a trial of therapy with this agent. The subcutaneous use of octreotide is of particular benefit to those patients with persistently high levels of growth hormone and IGF-I that cannot be suppressed by other means. Because acromegaly is relatively rare and complex, its diagnosis and treatment require the concerted efforts of an endocrinologist, an neurosurgeon and a radiation oncologist.


Assuntos
Acromegalia/diagnóstico , Acromegalia/terapia , Acromegalia/etiologia , Canadá , Humanos
5.
Hepatology ; 23(5): 1174-80, 1996 May.
Artigo em Inglês | MEDLINE | ID: mdl-8621151

RESUMO

Vasoactive intestinal peptide (VIP) blood levels in cirrhosis are elevated, but its hemodynamic and receptor characteristics remain unclarified. We aimed to quantify VIP receptor characteristics in mesenteric arteries, plasma VIP concentration by radioimmunoassay (RIA), and the hemodynamic effects of VIP infusion in bile duct-ligated (BDL) cirrhotic and sham-operated control rats. Mesenteric arterial membranes were prepared by ultracentrifugation, and receptor characteristics were studied using 125I-labeled VIP as a radioligand. For the hemodynamic study, there were four groups: cirrhotic and sham-operated rats were infused with either VIP (50 ng/kg/min for 15 minutes) or equivolumic isotonic saline. Regional blood flows were measured in conscious rats with radioactive microspheres. Receptor studies showed high- and low-affinity binding sites for VIP, which had similar equilibrium dissociation constants (binding affinities) and receptor densities for both the cirrhotic and control rats. Plasma VIP concentrations were significantly elevated in the cirrhotic rats. In both cirrhotic and sham-operated rats, VIP infusion produced plasma levels approximately twofold to threefold increased over the basal levels observed in cirrhotic rats. In cirrhotic rats, VIP infusion did not affect any hemodynamic parameter, whereas in the sham-operated rats VIP infusion significantly increased the mesenteric visceral blood flow. These results show that the hyporesponsiveness to VIP in cirrhotic rats is not attributable to receptor downregulation, implying postreceptor alterations. This suggests that VIP may not play a major role in the maintenance of splanchnic hyperemia in cirrhosis.


Assuntos
Hemodinâmica/efeitos dos fármacos , Cirrose Hepática Experimental/fisiopatologia , Artérias Mesentéricas/metabolismo , Receptores de Peptídeo Intestinal Vasoativo/metabolismo , Peptídeo Intestinal Vasoativo/farmacologia , Análise de Variância , Animais , Cirrose Hepática Experimental/metabolismo , Masculino , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/fisiopatologia , Radioimunoensaio , Ratos , Ratos Sprague-Dawley , Fluxo Sanguíneo Regional/efeitos dos fármacos , Peptídeo Intestinal Vasoativo/sangue , Peptídeo Intestinal Vasoativo/metabolismo
6.
Peptides ; 15(2): 383-5, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-8008642

RESUMO

Utilizing VIP and five VIP analogues, concentration-response curves for relaxation of rat mesenteric artery and rat gastric longitudinal muscle were determined for comparison with our previously published radioligand binding data on rat smooth muscle and other tissues. The biological potency of the VIP analogues in the present study compared more closely with their potency for VIP receptor binding in smooth muscle tissue (arteries) vs. other tissues (pituitary, brain, liver).


Assuntos
Relaxamento Muscular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Receptores de Peptídeo Intestinal Vasoativo/metabolismo , Peptídeo Intestinal Vasoativo/metabolismo , Animais , Relação Dose-Resposta a Droga , Fundo Gástrico/citologia , Masculino , Artéria Mesentérica Superior/citologia , Ratos , Receptores de Peptídeo Intestinal Vasoativo/classificação , Relação Estrutura-Atividade , Peptídeo Intestinal Vasoativo/análogos & derivados
7.
Peptides ; 14(4): 755-62, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-8234021

RESUMO

The pharmacological properties of the pituitary adenylate cyclase activating peptides (PACAPs) and vasoactive intestinal peptide (VIP) were compared using: (i) relaxation of vascular and gastric smooth muscle in vitro, and (ii) radioligand binding to membrane preparations of a variety of tissues. Vasoactive intestinal peptide and PACAP-27 were similarly potent in relaxing rat mesenteric arteries, porcine coronary arteries, and rat gastric smooth muscle, whereas PACAP-38 was either more or less potent than the other two peptides depending on the tissue model. Cross-desensitization to relaxation and radioligand binding studies of porcine coronary arteries suggested that VIP and the PACAPs interact with a common receptor in this tissue. A PACAP-preferring receptor with low affinity for VIP was identified in radioligand binding studies of rat brain and anterior pituitary. A second, nonselective, receptor that binds VIP and both PACAPs with high affinity was observed in preparations of rat and porcine arteries and rat lung, liver, brain, and anterior pituitary.


Assuntos
Relaxamento Muscular/efeitos dos fármacos , Neuropeptídeos/farmacologia , Receptores de Peptídeo Intestinal Vasoativo/metabolismo , Peptídeo Intestinal Vasoativo/farmacologia , Vasodilatadores/farmacologia , Animais , Ligação Competitiva/fisiologia , Masculino , Músculo Liso/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Neuropeptídeos/metabolismo , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase , Ratos , Peptídeo Intestinal Vasoativo/metabolismo , Vasodilatadores/metabolismo
8.
Life Sci ; 53(20): 1539-44, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-8105357

RESUMO

Whether somatostatin causes endothelium-dependent contraction (EDC) in isolated canine basilar arteries was examined. Somatostatin (10(-8)-10(-6) M) caused transient contractions in a dose-dependent manner. These contractions were abolished by removal of the endothelium, while the contractile response to neuropeptide Y occurred even after removal of the endothelium. The EDC induced by somatostatin (10(-7) M) was affected by neither atropine (10(-6) M) nor cyclo-somatostatin (10(-5) M), which suggests that the EDC is not due to release of endogenous acetylcholine and that the endothelial somatostatin receptor is different from hormonal somatostatin receptors. The somatostatin-induced EDC was attenuated by cyclooxygenase inhibitors (aspirin and indomethacin), thromboxane A2 (TXA2) synthetase inhibitors (OKY-064 and RS-5186), and TXA2 antagonists (ONO-3708 and S-145), which suggests that the endothelium-derived contracting factor is TXA2. These findings demonstrate that somatostatin causes EDC via activation of TXA2 synthesis in canine cerebral arteries.


Assuntos
Artérias Cerebrais/efeitos dos fármacos , Endotélio Vascular/metabolismo , Contração Muscular/efeitos dos fármacos , Contração Muscular/fisiologia , Músculo Liso Vascular/efeitos dos fármacos , Somatostatina/farmacologia , Tromboxano A2/biossíntese , Animais , Artérias Cerebrais/metabolismo , Artérias Cerebrais/fisiologia , Inibidores de Ciclo-Oxigenase/farmacologia , Cães , Endotélio Vascular/fisiologia , Feminino , Técnicas In Vitro , Inibidores de Lipoxigenase/farmacologia , Masculino , Músculo Liso Vascular/fisiologia , Somatostatina/análogos & derivados , Somatostatina/antagonistas & inibidores , Tromboxano A2/antagonistas & inibidores , Tromboxano-A Sintase/antagonistas & inibidores
9.
Pharmacology ; 42(5): 241-5, 1991.
Artigo em Inglês | MEDLINE | ID: mdl-1876608

RESUMO

Peptide histidine methionine (PHM) is a neuropeptide with structural homology to vasoactive intestinal peptide (VIP), itself a putative vasodilatory neurotransmitter. Intra-arterial administration of PHM caused a transient, dose-dependent increase in canine vertebral artery blood flow in vivo. PHM was less potent in this effect than VIP. The interaction of PHM with the vasoconstrictor amines, norepinephrine, histamine, and serotonin, was examined using isolated strips of the bovine middle cerebral artery. PHM shifted the concentration-response curves for vasocontraction by norepinephrine and histamine to the right but did not affect the vasocontraction induced by serotonin. These results suggest that PHM may have a role in the regulation of the cerebral circulation.


Assuntos
Circulação Cerebrovascular/efeitos dos fármacos , Peptídeo PHI/farmacologia , Artéria Vertebral/efeitos dos fármacos , Animais , Atropina/farmacologia , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Velocidade do Fluxo Sanguíneo/fisiologia , Burimamida/farmacologia , Bovinos , Cães , Relação Dose-Resposta a Droga , Histamina/farmacologia , Injeções Intra-Arteriais , Norepinefrina/farmacologia , Propranolol/farmacologia , Serotonina/farmacologia , Peptídeo Intestinal Vasoativo/farmacologia , Vasoconstrição/efeitos dos fármacos
10.
Peptides ; 11(6): 1157-61, 1990.
Artigo em Inglês | MEDLINE | ID: mdl-1965030

RESUMO

We investigated the effect of surgical castration of male rats on the binding of [Tyr(125I)10]VIP to receptors on the anterior pituitary gland, superior mesenteric artery, brain, liver, and prostate gland. In anterior pituitary membranes the maximum number of VIP binding sites was increased whereas binding affinity was decreased 24 hours following castration. In particular, the high affinity equilibrium dissociation constant (KD) increased from 0.13 +/- 0.02 nM (mean +/- SEM) to 0.67 +/- 0.07 nM and the maximum number of high affinity binding sites (Bmax) increased from 71 +/- 9 to 470 +/- 112 fmol/mg protein. No significant change was observed in the other tissues. Anesthesia or sham operation did not alter the anterior pituitary VIP receptor binding parameters. The changes in the VIP receptor 24 hours after castration were prevented by prior injection of testosterone. These findings demonstrate tissue-selective alterations to the anterior pituitary VIP receptor by castration that are likely mediated by withdrawal of testosterone.


Assuntos
Orquiectomia , Adeno-Hipófise/metabolismo , Receptores dos Hormônios Gastrointestinais/metabolismo , Peptídeo Intestinal Vasoativo/metabolismo , Animais , Ligação Competitiva/fisiologia , Encéfalo/metabolismo , Fígado/metabolismo , Masculino , Membranas/metabolismo , Artérias Mesentéricas/metabolismo , Próstata/metabolismo , Ensaio Radioligante , Ratos , Receptores de Peptídeo Intestinal Vasoativo , Sinaptossomos/metabolismo
11.
Peptides ; 11(5): 1015-20, 1990.
Artigo em Inglês | MEDLINE | ID: mdl-2178244

RESUMO

Vasoactive intestinal peptide (VIP) and peptide histidine isoleucine (PHI) are homologous neuropeptides with parallel biological actions. These similarities raise the question whether VIP and PHI have common or distinct mechanisms of action, including receptors. The present study attempted to distinguish specific binding sites for VIP and PHI in normal rat tissues using the homologous radioligands [Tyr(125I)10]VIP and [Tyr(125I)10]rat PHI. In rat brain, anterior pituitary, and liver membranes both radioligands identified a VIP-preferring receptor. Rat PHI had less than 10% the binding potency of VIP in these tissues irrespective of which radioligand was used. In rat uterine membranes [Tyr(125I)10]VIP bound to a receptor with approximately 100 times greater affinity for VIP over PHI. No specific binding of [Tyr(125I)10]rat PHI to rat uterus could be demonstrated. In conclusion, these results support the predominance of VIP-preferring receptors as opposed to PHI-preferring receptors in normal rat brain, anterior pituitary, liver and uterus.


Assuntos
Peptídeo PHI/metabolismo , Receptores dos Hormônios Gastrointestinais/metabolismo , Animais , Ligação Competitiva , Feminino , Fígado/metabolismo , Masculino , Especificidade de Órgãos , Adeno-Hipófise/metabolismo , Ratos , Receptores de Peptídeo Intestinal Vasoativo , Sinaptossomos/metabolismo , Útero/metabolismo
12.
Peptides ; 11(4): 667-72, 1990.
Artigo em Inglês | MEDLINE | ID: mdl-2172937

RESUMO

The regulation of female rat anterior pituitary vasoactive intestinal peptide (VIP) receptors was examined during postnatal development and lactation. VIP receptor binding to anterior pituitary membranes from 1- to 60-week-old rats and lactating rats was examined using HPLC purified [Tyr(125I)10]VIP. Nonlinear regression of competitive binding studies indicated the presence of 2 VIP binding sites in 3-week and older animals, whereas only 1 site was identified in 1- and 2-week-old rats. The single site did not differ significantly in affinity or number when compared to the low affinity site of older animals. The guanine nucleotide, GTP-gamma-S, decreased the specific binding of VIP by 60-80% in 3-week and older animals, but not in younger animals. Compared with adult nonlactating animals, the number of high affinity binding sites decreased significantly during lactation, with no change in receptor binding affinity.


Assuntos
Lactação/metabolismo , Adeno-Hipófise/metabolismo , Receptores dos Hormônios Gastrointestinais/metabolismo , Peptídeo Intestinal Vasoativo/metabolismo , Animais , Ligação Competitiva/fisiologia , Feminino , Adeno-Hipófise/crescimento & desenvolvimento , Ensaio Radioligante , Ratos , Receptores de Peptídeo Intestinal Vasoativo , Análise de Regressão
13.
Eur J Pharmacol ; 181(3): 199-205, 1990 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-2384132

RESUMO

The relaxant action of vasoactive intestinal peptide (VIP) was investigated using helical strips of four major branches of bovine coronary arteries. The concentration of VIP causing 50 percent of maximal relaxation ranged from 23 to 90 nM. Preincubation of arterial strips with VIP shifted the concentration-response curves for contractions elicited by potassium chloride or prostaglandin F2 alpha to the right. The relaxant effect of VIP was retained following removal of the vascular endothelium or in the absence of extracellular calcium. The structurally homologous peptides porcine and human peptide histidine isoleucine (PHI) were less potent than was VIP. It is concluded that there are functional receptors for VIP in bovine coronary arteries.


Assuntos
Músculo Liso Vascular/efeitos dos fármacos , Peptídeo Intestinal Vasoativo/farmacologia , Animais , Cálcio/fisiologia , Bovinos , Vasos Coronários/efeitos dos fármacos , Dinoprosta/farmacologia , Endotélio Vascular/efeitos dos fármacos , Técnicas In Vitro , Relaxamento Muscular/efeitos dos fármacos , Peptídeo PHI/farmacologia , Cloreto de Potássio/farmacologia
14.
Mol Pharmacol ; 37(6): 971-7, 1990 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-2163020

RESUMO

The structure-activity relationships for vasoactive intestinal peptide (VIP) receptor binding were studied using N-terminally modified VIP analogs. VIP fragments, and VIP receptor antagonists. Tissue sources included bovine coronary artery, rat mesenteric artery, rat pituitary, rat brain synaptosomes, and rat liver. Experimental conditions for receptor binding were maintained as near to identical as possible. The competitive binding curves for VIP analogs were similar in the bovine and rat vascular preparations. However, appreciable differences were observed between the vascular and other preparations. The vascular receptors discriminated between [D-His1]VIP and [Phe1]VIP, whereas the receptors in other tissues did not. The greatest selectivity was found for [D-Ala4]VIP, which was among the lowest affinity analogs tested on the vasculature but among the highest affinity analogs in the other preparations. The rank orders of analog potencies were comparable for the rat brain and pituitary receptors. The rat liver VIP receptor differed from its counterpart in brain and pituitary predominantly by discriminating between [D-Phe2]VIP and [D-Arg2]VIP. The two VIP receptor antagonists bound weakly and nonselectively to all receptor preparations. Integrity of the full VIP molecule was necessary for full potency of binding to the vascular receptor. We conclude that the vascular VIP receptor possesses recognition properties that are distinct from those for VIP receptors in liver, pituitary, or brain.


Assuntos
Encéfalo/metabolismo , Fígado/metabolismo , Receptores dos Hormônios Gastrointestinais/metabolismo , Peptídeo Intestinal Vasoativo/metabolismo , Animais , Ligação Competitiva , Encéfalo/efeitos dos fármacos , Bovinos , Fígado/efeitos dos fármacos , Masculino , Especificidade de Órgãos , Ratos , Ratos Endogâmicos , Receptores dos Hormônios Gastrointestinais/efeitos dos fármacos , Receptores de Peptídeo Intestinal Vasoativo , Relação Estrutura-Atividade , Sinaptossomos/efeitos dos fármacos , Sinaptossomos/metabolismo
15.
Endocrinology ; 126(4): 1981-8, 1990 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-2156675

RESUMO

Vasoactive intestinal peptide (VIP) has been implicated as a physiological PRL-releasing factor; however, characterization of VIP receptors on normal pituitaries using radioligand-binding methods has been problematic. In this study we demonstrated specific receptors for VIP in anterior pituitary glands of female rats using HPLC-purified monoiodinated [Tyr(125I)10]VIP. Binding of VIP was reversible, saturable to receptor and radioligand, regulated by guanine nucleotides, and dependent on time and temperature. Scatchard analysis of competitive binding studies indicated high and low affinity binding sites, with equilibrium dissociation constants (Kd) of 0.19 +/- 0.03 and 28 +/- 16 nM, respectively. The corresponding maximum numbers of binding sites were 158 +/- 34 fmol/mg and 11.7 +/- 6.9 pmol/mg. Binding was specific, as peptides with structural homology to VIP were less than 100th as potent as VIP. The rank order of potency of the peptides tested was VIP greater than rat (r) peptide histidine isoleucine = human (h) PHI greater than rGRF greater than bovine GRF = porcine PHI = VIP-(10-28) greater than hGRF greater than secretin greater than apamin greater than glucagon. Radioligand binding was associated primarily with lactotrope-enriched fractions prepared by unit gravity sedimentation of dispersed anterior pituitary cells. VIP stimulated PRL release from cultured rat anterior pituitary cells, with an ED50 of 1 nM. These results, comprising the first identification of specific VIP receptors in normal rat anterior pituitary tissue using radioligand-binding methods, provide additional support for a biological role of VIP in lactotrope function.


Assuntos
Adeno-Hipófise/metabolismo , Prolactina/metabolismo , Receptores dos Hormônios Gastrointestinais/metabolismo , Animais , Feminino , Radioisótopos do Iodo , Adeno-Hipófise/citologia , Radioimunoensaio , Ratos , Ratos Endogâmicos , Receptores de Peptídeo Intestinal Vasoativo , Distribuição Tecidual , Tirosina/metabolismo , Peptídeo Intestinal Vasoativo/metabolismo
16.
Acta Neurochir (Wien) ; 104(1-2): 42-7, 1990.
Artigo em Inglês | MEDLINE | ID: mdl-2201171

RESUMO

We have studied the effect of endothelin, an endothelium-derived peptide, on isolated canine and bovine cerebral arteries in vitro and on canine vertebral blood flow (VBF) in vivo. Endothelin produced a dose-dependent contraction of canine and bovine arterial smooth muscle with ED50 values ranging from 4 to 8 nM. The response to endothelin developed slowly and persisted as a sustained contraction. Maximal contraction by endothelin required the presence of extracellular calcium and was independent of the presence of endothelium. The maximal contraction produced by endothelin was approximately 2-3 times greater than that produced by neuropeptide Y or angiotensin II. The injection of endothelin into the vertebral artery decreased vertebral blood flow (VBF) dose-dependently without affecting systemic blood pressure or heart rate. The decrease in VBF produced by endothelin was long-lasting, like that produced by neuropeptide Y, but more potent. The present data, together with our previous study demonstrating that the intracisternal injection of endothelin induces an unusually long-lasting decrease in the basilar artery diameter angiographically, suggests that endothelin may act as a long-lasting vasoconstrictor in cerebral vascular disease.


Assuntos
Artérias Cerebrais/fisiologia , Endotélio Vascular/fisiologia , Contração Muscular/efeitos dos fármacos , Músculo Liso Vascular/fisiologia , Peptídeos/farmacologia , Vasoconstrição/efeitos dos fármacos , Artéria Vertebral/fisiologia , Angiotensina II/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Bovinos , Artérias Cerebrais/efeitos dos fármacos , Cães , Endotelinas , Feminino , Frequência Cardíaca/efeitos dos fármacos , Técnicas In Vitro , Masculino , Músculo Liso Vascular/efeitos dos fármacos , Neuropeptídeo Y/farmacologia , Fluxo Sanguíneo Regional/efeitos dos fármacos , Artéria Vertebral/efeitos dos fármacos
17.
Peptides ; 10(5): 993-1001, 1989.
Artigo em Inglês | MEDLINE | ID: mdl-2558369

RESUMO

Vasoactive intestinal peptide (VIP) and peptide histidine isoleucine (PHI) are homologous neuropeptides which share vasodilatory properties. This paper addresses the question of whether PHI exerts its vascular action via a receptor distinct from that for VIP. Radioligand binding experiments were done using [Tyr(125I)10]VIP, [Tyr(125I)22]porcine PHI, [Tyr(125I)10]rat PHI and arterial preparations from rat, bovine and porcine species. The radioiodination of rat PHI by the lactoperoxidase-glucose oxidase method and analysis of the structure of the major radiolabeled derivatives were described. All the receptor binding experiments identified a VIP-preferring receptor irrespective of which radioligand or arterial preparation was utilized. VIP and PHI peptides demonstrated cross-desensitization in studies of relaxation of porcine coronary arterial strips in vitro. The present results favor the conclusion that the vascular actions of the PHI peptides are best explained by binding to a VIP-preferring receptor.


Assuntos
Peptídeo PHI/fisiologia , Receptores dos Hormônios Gastrointestinais/fisiologia , Peptídeo Intestinal Vasoativo/metabolismo , Vasodilatação/fisiologia , Sequência de Aminoácidos , Animais , Ligação Competitiva/fisiologia , Bovinos , Vasos Coronários/fisiologia , Humanos , Técnicas In Vitro , Artérias Mesentéricas/metabolismo , Dados de Sequência Molecular , Peptídeo PHI/metabolismo , Ensaio Radioligante , Ratos , Receptores dos Hormônios Gastrointestinais/metabolismo , Receptores de Peptídeo Intestinal Vasoativo , Suínos
18.
Can J Physiol Pharmacol ; 67(8): 851-6, 1989 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-2557141

RESUMO

Previous studies have demonstrated a specific vascular receptor for the neurotransmitter peptide, vasoactive intestinal peptide (VIP), and have suggested that the receptor is positively coupled to vascular adenylate cyclase. The present study addressed the questions whether the vascular VIP receptor is subject to regulation by guanine nucleotides and whether a disulfide reducing agent, dithiothreitol, would perturb the binding function of the vascular VIP receptor. Guanosine triphosphate (GTP) and its non-hydrolyzable analogs, guanylyl imidodiphosphate (Gpp(NH)p) and guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma-S), increased the rate of dissociation of radiolabeled VIP from arterial receptors in a concentration-dependent manner. GTP-gamma-S increased the equilibrium dissociation constant (KD) of the high affinity vascular VIP binding site, a result consistent with decreased high affinity binding of VIP induced by GTP-gamma-S. These results are consistent with a regulatory role for guanine nucleotides in the function of the vascular VIP receptor. The disulfide reducing agent, dithiothreitol, caused a decrease in specific binding of radiolabeled VIP. Upon Scatchard analysis the effect of dithiothreitol was characterized by an increase in the KD and a decrease in the maximum number of binding sites (Bmax) of the high affinity binding site. These results suggest that disulfide bonds are important for ligand binding to vascular VIP receptors. The sulfhydryl alkylating agents, N-ethylmaleimide and iodoacetamide, had minimal effects on radioligand binding.


Assuntos
Ditiotreitol/farmacologia , Receptores dos Hormônios Gastrointestinais/efeitos dos fármacos , Animais , Ligação Competitiva , Bovinos , Dissulfetos/metabolismo , Guanosina Trifosfato/análogos & derivados , Guanosina Trifosfato/farmacologia , Guanilil Imidodifosfato/farmacologia , Ligação Proteica/efeitos dos fármacos , Ratos , Ratos Endogâmicos , Receptores dos Hormônios Gastrointestinais/metabolismo , Receptores de Peptídeo Intestinal Vasoativo , Compostos de Sulfidrila/metabolismo , Tionucleotídeos/farmacologia , Peptídeo Intestinal Vasoativo/metabolismo
19.
Brain Res ; 457(2): 241-5, 1988 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-3219552

RESUMO

The natural product, forskolin, which stimulates adenylate cyclase by a direct, non-receptor-mediated mechanism, was studied for its effect on the tension of isolated brain arteries and adenylate cyclase activity of cerebral arteries. Helical strips of bovine and porcine basilar arteries and bovine middle cerebral arteries, which had been precontracted with prostaglandin F2 alpha (PGF2 alpha) or KCl, relaxed potently to administration of forskolin with ED50 values, ranging from 22 to 69 nM. Incubation of forskolin with a broken cell preparation of bovine cerebral arteries resulted in an efficacious stimulation of adenylate cyclase, approximating 5 times basal activity at a forskolin concentration of 1 microM. The metal salts nickel chloride and manganese chloride decreased the potency of vasorelaxation by vasoactive intestinal peptide (VIP), which stimulates adenylate cyclase via the VIP receptor. In contrast, nickel chloride had little effect on vasorelaxation by forskolin. The endogenous nucleoside, adenosine, which acts via the adenosine receptor and adenylate cyclase, relaxed bovine basilar and middle cerebral arteries with ED50 values ranging from 0.26 to 0.94 microM. The data presented support a role for adenylate cyclase in mediating vasodilation of brain blood vessels.


Assuntos
Adenilil Ciclases/metabolismo , Artérias Cerebrais/efeitos dos fármacos , Colforsina/farmacologia , Contração Muscular/efeitos dos fármacos , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Animais , Artéria Basilar/efeitos dos fármacos , Artéria Basilar/enzimologia , Química Encefálica , Bovinos , Artérias Cerebrais/enzimologia , Técnicas In Vitro , Suínos
20.
J Recept Res ; 8(6): 831-8, 1988.
Artigo em Inglês | MEDLINE | ID: mdl-2848123

RESUMO

This study examined the utility of four polycationic agents for treating glass fibre filters used in the receptor binding assay for vasoactive intestinal peptide (VIP). Polyethylenimine (PEI), polybrene, protamine and methylated bovine serum albumin proved satisfactory in terms of low filter binding of free radioligand and retention of membrane-bound radioligand. Their performance was superior or comparable to untreated Millipore EGWP cellulose acetate filters which we had previously utilized but which are no longer manufactured. The results with polycations indicate the importance of ionic interactions between filter, biological membranes and radioligand in determining the performance of a filtration assay for radioligand-receptor binding. At a practical level, PEI has the disadvantage of potential toxicity. The satisfactory performance of the other polycations indicates that they provide safer alternatives to PEI for filtration assay of the VIP receptor and possibly receptors for other basic ligands.


Assuntos
Poliaminas , Polímeros/farmacologia , Ensaio Radioligante/métodos , Receptores dos Hormônios Gastrointestinais/análise , Animais , Bovinos , Filtração/instrumentação , Polieletrólitos , Receptores de Peptídeo Intestinal Vasoativo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...