Noradrenaline modulates the spontaneous firing activities of Purkinje cells via α2-adrenergic receptor in mouse cerebellar cortex / 生理学报

Cerebellar Purkinje cells (PCs) exhibit two types of discharge activities: simple spike (SS) and complex spike (CS). Previous studies found that noradrenaline (NA) can inhibit CS and bidirectionally regulate SS, but the enhancement of NA on SS is overwhelmed by the strong inhibition of excitatory molecular layer interneurons. However, the mechanism underlying the effect of NA on SS discharge frequency is not clear. Therefore, in the present study, we examined the mechanism underlying the increasing effect of NA on SS firing of PC in mouse cerebellar cortex in vivo and in cerebellar slice by cell-attached and whole-cell recording technique and pharmacological methods. GABAA receptor was blocked by 100 µmol/L picrotoxin in the whole process. In vivo results showed that NA significantly reduced the number of spikelets of spontaneous CS and enhanced the discharge frequency of SS, but did not affect the discharge frequency of CS. In vitro experiments showed that NA reduced the number of CS spikelets and after hyperpolarization potential (AHP) induced by electrical stimulation, and increased the discharge frequency of SS. NA also reduced the amplitude of excitatory postsynaptic current (EPSC) of parallel fiber (PF)-PC and significantly increased the paired-pulse ratio (PPR). Application of yohimbine, an antagonist of α2-adrenergic receptor (AR), completely eliminated the enhancing effect of NA on SS. The α2-AR agonist, UK14304, also increased the frequency of SS. The β-AR blocker, propranolol, did not affect the effects of NA on PC. These results suggest that in the absence of GABAA receptors, NA could attenuate the synaptic transmission of climbing fiber (CF)-PC via activating α2-AR, inhibit CS activity and reduce AHP, thus enhancing the SS discharge frequency of PC. This result suggests that NA neurons of locus coeruleus can finely regulate PC signal output by regulating CF-PC synaptic transmission.

Renal sympathetic nerve activation via α₂-adrenergic receptors in chronic kidney disease progression

Chronic kidney disease (CKD) is increasing worldwide without an effective therapeutic strategy. Sympathetic nerve activation is implicated in CKD progression, as well as cardiovascular dysfunction. Renal denervation is beneficial for controlling blood pressure (BP) and improving renal function through reduction of sympathetic nerve activity in patients with resistant hypertension and CKD. Sympathetic neurotransmitter norepinephrine (NE) via adrenergic receptor (AR) signaling has been implicated in tissue homeostasis and various disease progressions, including CKD. Increased plasma NE level is a predictor of survival and the incidence of cardiovascular events in patients with end-stage renal disease, as well as future renal injury in subjects with normal BP and renal function. Our recent data demonstrate that NE derived from renal nerves causes renal inflammation and fibrosis progression through alpha-2 adrenergic receptors (α₂-AR) in renal fibrosis models independent of BP. Sympathetic nerve activation-associated molecular mechanisms and signals seem to be critical for the development and progression of CKD, but the exact role of sympathetic nerve activation in CKD progression remains undefined. This review explores the current knowledge of NE-α₂-AR signaling in renal diseases and offers prospective views on developing therapeutic strategies targeting NE-AR signaling in CKD progression.

The Alpha-2A Adrenergic Receptor Gene -1291C/G Single Nucleotide Polymorphism is Associated with the Efficacy of Methylphenidate in Treating Taiwanese Children and Adolescents with Attention-Deficit Hyperactivity Disorder

OBJECTIVE: The therapeutic effect of methylphenidate (MPH) in treating attention-deficit/hyperactivity disorder (ADHD) has been related to the alpha-2A adrenergic receptor (ADRA2A) gene -1291C/G single nucleotide polymorphism (SNP). We investigated the effect of MPH in treating Taiwanese children and adolescent with ADHD and its relation to the ADRA2A gene -1291C/G SNP. METHODS: The subjects with DSM-IV ADHD diagnosis underwent a titration period to find out the dose of MPH for maintenance treatment. After 4 weeks maintenance treatment, the effect of MPH was evaluated by the Swanson, Nolan and Pelham version IV total scores. The subjects with more than 25% score reduction were referred to responders and those with ≥50% improvement were considered as better responders. The -1291C/G variant of the ADRA2A gene was identified by DNA sequencing and what relevance it has to the MPH response was examined by binary logistic regression analysis. RESULTS: Of the 59 subjects, 44 (74.6%) were responsive to MPH treatment and the responsiveness was not shown to be associated with the ADRA2A gene -1291C/G SNP. As the responsive subjects were categorized as moderate responders and better responders and subjected to statistical analysis, the GG homozygotes showed a greater chance to have a better response to MPH treatment than CC homozygotes (p=0.02), with an odds ratio of 32.14 (95% CI=1.64–627.80). CONCLUSION: The ADRA2A gene -1291C/G SNP is associated with the efficacy of MPH for the treatment of ADHD in Taiwanese children and adolescents. The responsive subjects bearing homozygous -1291G allele are more likely to have a better response to MPH treatment.

Dexmedetomidine as an anesthetic adjuvant in cardiac surgery: a cohort study

ABSTRACT Objective: α-2-agonists cause sympathetic inhibition combined with parasympathetic activation and have other properties that could be beneficial during cardiac anesthesia. We evaluated the effects of dexmedetomidine as an anesthetic adjuvant compared to a control group during cardiac surgery. Methods: We performed a retrospective analysis of prospectively collected data from all adult patients (> 18 years old) undergoing cardiac surgery. Patients were divided into two groups, regarding the use of dexmedetomidine as an adjuvant intraoperatively (DEX group) and a control group who did not receive α-2-agonist (CON group). Results: A total of 1302 patients who underwent cardiac surgery, either coronary artery bypass graft or valve surgery, were included; 796 in the DEX group and 506 in the CON group. Need for reoperation (2% vs. 2.8%, P=0.001), type 1 neurological injury (2% vs. 4.7%, P=0.005) and prolonged hospitalization (3.1% vs. 7.3%, P=0.001) were significantly less frequent in the DEX group than in the CON group. Thirty-day mortality rates were 3.4% in the DEX group and 9.7% in the CON group (P<0.001). Using multivariable Cox regression analysis with in hospital death as the dependent variable, dexmedetomidine was independently associated with a lower risk of 30-day mortality (odds ratio [OR]=0.39, 95% confidence interval [CI]: 0.24-0.65, P≤0.001). The Logistic EuroSCORE (OR=1.05, 95% CI: 1.02-1.10, P=0.004) and age (OR=1.03, 95% CI: 1.01-1.06, P=0.003) were independently associated with a higher risk of 30-day mortality. Conclusion: Dexmedetomidine used as an anesthetic adjuvant was associated with better outcomes in patients undergoing coronary artery bypass graft and valve surgery. Randomized prospective controlled trials are warranted to confirm our results.

Genetic Variations in Attention Deficit Hyperactivity Disorder Subtypes and Treatment Resistant Cases

OBJECTIVE: ObjectiveaaWe evaluated the distribution of alpha-2A adrenergic receptor (ADRA2A) and catechol-o-methyltransferase (COMT) single nucleotide polymorphisms (SNPs) among ADHD subtypes and other homogeneous patient populations including treatment-resistant cases and patients with high symptom severity. METHODS: Methodsaa121 ADHD patients aged 6-18 years were included in the study. Diagnosis and subtypes designation were confirmed using the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS) and symptoms were evaluated using the Conners' Parent (CPRS) and Teacher Rating Scales (CTRS). The response to methylphenidate was assessed objectively using the Clinical Global Impression-Severity Scale (CGI-S) and Global Assessment of Functioning Scale (GAS) as well as the Continuous Performance (CPT) and Trail Making tests (TMT-A, B). Patients were genotyped for ADRA2A (rs1800544) and COMT (rs4680) SNPs by PCR/RFLP and compared to a gender-matched control group. RESULTS: Although there was no association of COMT (rs4680) SNP with symptoms or diagnosis, the ADRA2A polymorphism, low socioeconomic status (SES), and comorbid psychiatric diagnosis were all associated with poor response to methylphenidate in logistic regression analysis. CONCLUSION: Clinicians may consider adjuvant strategies when these negative factors are present to increase the success of tailored ADHD treatments in the future.

Effect of dexmedetomidine hydrochloride on H2O2-induced oxidative stress and inflammatory response in Kupffer cells / 中南大学学报(医学版)

OBJECTIVE@#To evaluate whether dexmedetomidine hydrochloride, an α(2)-adrenergic receptor agonist, can prevent H(2)O(2)-induced oxidative stress and inflammatory response in Kupffer cells.
@*METHODS@#H(2)O(2)-induced oxidative damage model of Kupffer cell was established. Kupffer cells were pre-conditioned by dexmedetomidine hydrochloride or Yohimbine for 24 h. MTT colorimetry was used to demonstrate the survival rate of Kupffer cells. The levels of lactate dehydrogenase (LDH), malonaldehyde (MDA) and TNF-α in the culture medium were assessed by corresponding kits.
@*RESULTS@#Dexmedetomidine hydrochloride protected Kupffer cells from H(2)O(2)-induced oxidative damage, showing an increase in the cell survival rate while a decrease in LDH, MDA and TNF-α release in the culture supernatant. Yohimbine, an α(2)-adrenergic receptor antagonist, completely neutralized the protective effect of Dexmedetomidine hydrochloride on Kupffer cells. Yohimbine itself had no effect on H(2)O(2)-induced oxidative damage and inflammatory response.
@*CONCLUSION@#Dexmedetomidine hydrochloride can prevent H(2)O(2)-induced oxidative stress and inflammatory response in Kupffer cells through activation of α(2)-adrenergic receptors.

Antiallodynic effects of intrathecal tianeptine in a neuropathic pain rat

BACKGROUND: Tianeptine is an antidepressant drug which is used for treating depression. Interestingly, the tianeptine has shown antinociceptive effects within a variety of nociceptions. The aim of this study is to investigate the antiallodynic effects of tianeptine in neuropathic pain rats and also determine the involvements of serotonergic, alpha-2 adrenergic and adenosine receptors at the spinal level. METHODS: Neuropathic pain was induced by ligation of left lumbar at 5th and 6th spinal nerves in male Sprague-Dawley rats. PE-10 catheters were placed into the thoracolumbar subarachnoid space for drug injections. Mechanical allodynia was evaluated by measuring the withdrawal threshold to von Frey filament when applying on the plantar surface of rats. The effects of intrathecal tianeptine were observed at 15, 30, 60, 90, 120, 150, 180 minutes after delivery. Antagonists for serotonergic (dihydroergocristine), alpha-2 adrenergic (yohimbine) and adenosine (CGS 15943) receptors were intrathecally administered 10 minutes prior to tianeptine in order to evaluate the involvement of both receptors. RESULTS: Intrathecal tianeptine increased dose-dependently at the withdrawal threshold in the ligated paw. Pretreatment with intrathecal dihydroergocristine, yohimbine and CGS 15943 antagonized the antiallodynic effects of tianeptine. CONCLUSIONS: These results suggested that intrathecal tianeptine attenuates the spinal nerve ligation induced tactile allodynia. Serotonergic, alpha-2 adrenergic and adenosine receptors are all involved in the antiallodynic effects of tianeptine at the spinal level.

Differential expression of alpha-adrenoceptor subtypes in rat dorsal root ganglion after chronic constriction injury / 华中科技大学学报（医学）（英德文版）

mRNAs of alpha-adrenoceptor (α-AR) subtypes are found in neurons in dorsal root ganglion (DRG) and change after peripheral nerve injury. In this study, the distribution of α-AR subtype proteins was studied in L5 DRG of normal rats and rats with chronic constriction injury of sciatic nerve (CCI). Using immunofluorescence technique, it was found that α1A-, α1B-, and α2A-AR proteins were expressed in large, medium, and small size neurons in normal DRG, and significantly increased in all size neurons 14 days after CCI. α1D- and α2C-AR was also expressed in all size neurons in normal DRG. However, α1D-AR was significantly increased and α2C-AR was decreased in small size neurons 14 days post CCI. α2B-AR neurons were not detectable in normal and CCI DRG. Co-expression of α1A- and α2A-AR in the same neuron was observed in normal DRG and increased post CCI. Collectively, these results indicated that there is distinct distribution of α-AR subtypes in DRG neurons, and the distribution and levels of expression of α-AR subtypes change differently after CCI. The up-regulation of α-AR subtypes in DRG neurons may play an important role in the process of generating and transmitting neuropathic pain.

The expression of α2A-adrenoceptors in the calcium-binding protein immunoreactive interneurons in rat prefrontal cortex / 生理学报

The α2A adrenoceptors (α2A-ARs) are the most common adrenergic receptor subtype found in the prefrontal cortex (PFC). It is generally accepted that stimulation of postsynaptic α2A-ARs on pyramidal neurons are key to PFC functions, such as working memory. However, the expression of α2A-ARs in interneurons is largely unknown. In the present study using double-labeling immunofluorencence technique, we investigated the expression of α2A-ARs in major types of rat PFC interneurons expressing calcium-binding proteins parvalbumin (PV), calretinin (CR), and calbindin (CB). Our data demonstrated that α2A-ARs are highly expressed in calcium-binding protein immunoreactive interneurons of rat PFC, suggesting that stimulation of α2A-ARs may alter neural networks comprising pyramidal neurons and interneurons, thereby exerting a beneficial effect on PFC cognitive functions. The present study provides the morphological basis for a potential mechanism by which stimulation of α2A-ARs induces cognitive improvement.

The correlation research between the polymorphism of genotype of site-1296 in alpha2A-AR receptor gene and the susceptibility of vestibular function / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate the correlation between the polymorphism of genotype of site-1296 in alpha2A-AR receptor gene and the susceptibility of vestibular function.@*METHOD@#Ninety-four blood samples were collected from pilot cadets, consisting of susceptible and tolerance groups to vestibular function. Genomic DNA was isolated, and the coding region of alpha2A-AR receptor gene was amplified by polymerase chain reaction (PCR). The PCR products were analyzed by gene sequencing. Gene frequency was calculated, and, the coincidence between the polymorphism of alpha2A-AR receptor gene in the groups and Hardy-Weinberg balance was evaluated. The allele frequency of the two groups was compared by Chi square test.@*RESULT@#G/C polymorphism was existed in Site-1296 of alpha2A-AR gene regulation zone, including GG, GC, CC. The express of GG Genotype in susceptible group exceeded that of the other group. There were significance differences in both genotype constituent ratio and alleles frequency of the two groups.@*CONCLUSION@#The polymorphism of genotype of site-1296 in alpha2A-AR receptor gene is possibly correlated with the susceptibility to vestibular function.

Regional Brain Perfusion before and after Treatment with Methylphenidate According to the MspI Polymorphism of the Alpha-2A Adrenergic Receptor Gene in Children with Attention-Deficit Hyperactivity Disorder

OBJECTIVES: Dysregulation of the central noradrenergic system may be involved in the pathophysiology of attention-deficit hyperactivity disorder (ADHD). The aim of this study was to examine the differences in pre- and post-treatment cerebral perfusion according to the MspI polymorphisms of the alpha-2A-adrenergic receptor gene (ADRA2A) in children with ADHD. METHODS: Thirty seven drug-naive ADHD children (8.9+1.8 years old, M=32, F=5) were genotyped. Baseline single-photon emission computed tomography (SPECT) and clinical assessments were performed for ADHD children. After treatment with methylphenidate for eight weeks, SPECT and clinical assessment were repeated. RESULTS: No differences in baseline clinical assessments or cerebral perfusion were observed according to the MspI genotype. However, after treatment, ADHD children with the G/G genotype at the MspI polymorphism showed hyperperfusion in the right cerebellar declive (p=.001, uncorrected) and hypoperfusion in the left lentiform nucleus and left cingulate gyrus (p<.001 and p=.001, uncorrected), compared to children without the G/G genotype. CONCLUSION: Although the results of this study should be interpreted cautiously, they suggest a possible role of the MspI polymorphisms of the ADRA2A gene in methylphenidate-induced changes in cerebral perfusion.

The role of spinal adrenergic receptors on the antinociception of ginsenosides in a rat postoperative pain model / 대한마취과학회지

BACKGROUND: The effect of spinal adrenergic and cholinergic receptors on the anti-nociceptive effect of intrathecal ginsenosides was determined in a rat postoperative pain model. METHODS: Catheters were placed into the intrathecal space of male Sprague-Dawley rats. Postoperative pain was evoked by an incision to the plantar surface of a hind paw. Withdrawal thresholds was used as a nociceptive parameter and was measured with a von Frey filament. After observing the effect of intrathecal ginsenosides, an alpha-1 adrenergic receptor antagonist (prazosin), an alpha-2 adrenergic receptor antagonist (yohimbine), a muscarinic acetylcholine receptor antagonist (atropine), and a nicotinic acetylcholine receptor antagonist (mecamylamine) were given 10 min before administration of the ginsenosides to analyze the contribution of spinal adrenergic and cholinergic receptors on the antinociceptive effect of ginsenosides. RESULTS: Paw incision decreased withdrawal threshold in incised site of paw, but no change of withdrawal threshold was not seen in non-incised site. The intrathecal ginsenosides increased withdrawal threshold of the incised paw in a dose-dependent manner. Pre-treatment with both prazosin and intrathecal yohimbine antagonized the anti-nociceptive effect of the ginsenosides. However, pre-treatments with atropine or mecamylamine had any effect on the antinociceptive activity of ginsenosides. CONCLUSIONS: Intrathecal ginsenosides are effective in attenuation of postoperative pain induced in the rat model. Anti-nociceptive action of ginsenosides is partially mediated by spinal adrenergic receptors, but does not appear to be related to spinal cholinergic receptors.

Effect of dexmedetomidine hydrochloride on H2O2-induced oxidative stress in alveolar macrophages / 中南大学学报(医学版)

OBJECTIVE@#To evaluate whether dexmedetomidine hydrochloride, an α2-adrenergic receptor agonist, can prevent oxidative damage to alveolar macrophages induced by H2O2.@*METHODS@#We used methyl thiazolyl tetrazolium (MTT) colorimetry to test the effect of different concentrations and action time of H2O2 on the survival rate of alveolar macrophages, and then we chose the appropriate H2O2 concentration and action time to build NR8383 cell oxidative damage model. After pre-conditioning of 0.01, 0.10, and 1.00 μmol/L dexmedetomidine hydrochloride for 24 hours, MTT colorimetry was used to demonstrate the survival rate of NR8383 cells damaged by H2O2, and the release of lactate dehydrogenase (LDH) and TNF-α by H2O2-damaged NR8383 cells was detected by corresponding kit.@*RESULTS@#At 50-300 μmol/L, H2O2 caused concentration-dependent oxidative damage in the alveolar macrophages, decreased the cell survival rate, and increased LDH and TNF-α release. At 0.01-1.00 μmol/L dexmedetomidine hydrochloride concentration-dependently protected NR8383 cells from oxidative damage induced by H2O2, significantly increased the cell survival rate, decreased LDH and TNF-α release, and this effect of dexmedetomidine hydrochloride was dose-dependent. Yohimbine, an α2 - adrenergic receptor antagonist, completely neutralized the protective effect of dexmedetomidine hydrochloride on NR8383 cells without affecting the oxidative damage of NR8383 cells.@*CONCLUSION@#Dexmedetomidine hydrochloride can prevent alveolar macrophages from oxidative damage induced by H2O2, which may play a protective role through α2 - adrenergic receptors.

Yohimbine protects against endotoxin-induced acute lung injury by blockade of alpha 2A adrenergic receptor in rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Alpha 2A adrenergic receptor (AR) is a subtype of α2 AR belonging to G protein-coupled receptors, and exerts a variety of biological effects. Recent studies have demonstrated that the α2A AR activation was closely related with inflammatory reaction. The present study aimed to investigate the influence of α2A AR antagonist, yohimbine, on the severity of endotoxin-induced acute lung injury in rats.</p><p><b>METHODS</b>A total of 72 male Sprague-Dawley rats were randomly divided into three groups: control group, lipopolysaccharide (LPS) group and LPS + yohimbine group. Rats were intratracheally administrated with normal saline or LPS (300 µg), and the rats in the LPS + yohimbine group were treated with additional yohimbine (2 mg/kg, i.p) soon after LPS administration. Six, 24 and 48 hours after treatment, arterial blood gas analysis was carried out, and optical microscopy was performed to evaluate pathological changes in the lung, and lung injury score was assessed. The count of white blood cells in bronchoalveolar lavage fluid (BALF) was determined. The levels of norepinephrine, tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in BALF were measured with enzyme-linked immunosorbent assay. Immunocytochemistry was performed for the detection of α2A AR on inflammatory cells in BALF.</p><p><b>RESULTS</b>When compared with the control group, the oxygenation index in the LPS group was significantly decreased, and white blood cell count, the lung histopathological scores, levels of norepinephrine and IL-6 as well as α2A AR expression on inflammatory cells in the BALF were dramatically increased at different time points, and the concentrations of TNF-α and IL-1β were also increased except at 48 hours after LPS administration. The oxygenation index decreased while white blood cell count in BALF and the lung histopathological scores were obviously increased in the LPS + yohimbine group. The level of norepinephrine in BALF was increased at each time interval in the LPS + yohimbine group, and so did the levels of TNF-α, IL-1β and IL-6 at 6 and 48 hours after LPS administration respectively. When compared with the LPS group, the oxygenation index, white blood cell count, the lung histopathological scores and the level of IL-6 in the LPS + yohimbine group were significantly improved at each time interval, and the concentrations of TNF-α and IL-1β were also lower at 24 hours of LPS administration (all P < 0.05). Correlation analysis indicated the level of norepinephrine was related to the levels of TNF-α, IL-1β and IL-6 in the BALF and the lung histopathological scores (r = 0.703, r = 0.595, r = 0.487 and r = 0.688, respectively, P < 0.001) and the intensity scores of immunoreactivity to α2A AR on inflammatory cells were also associated with the levels of TNF-α, IL-1β and IL-6 as well as the lung histopathologial scores (r = 0.803, r = 0.978, r = 0.716 and r = 0.808, respectively, P < 0.001).</p><p><b>CONCLUSIONS</b>Yohimbine can inhibit TNF-α, IL-1β and IL-6 overproduction and relieve the severity of pulmonary inflammation induced by endotoxin, which is maybe mediated by blockade of α2A AR on inflammatory cells.</p>

Effects in Lumen Width of Nasolacrimal Drainage System After Adrenergic Drug Irrigation

PURPOSE: The lacrimal sac and nasolacrimal duct are surrounded by a wide cavernous system of veins and arteries, and the blood vessels of the cavernous body are innnervated by the autonomic nervous system. The purpose of this study was to determine the effect of an adrenergic agonist on the lumen width of the nasolacrimal drainage system. METHODS: Dacryocystography was performed on 35 patients with only epiphora and not nasolacrimal duct obstruction. The anteroposterior (AP) diameters and the oblque diameters of the nasolacrimal ducts were measured. Next, 18 patients were infused with 0.5 ml Alphagan-P(R) (alpha-2 adrenergic receptor agonist), 17 patients were infused with 0.5 ml DL methylephedrine hydrochloride (alpha-1 and alpha-2 adrenergic receptor agonist), and dacryocystography was performed again to determine the change in the lumen width of the nasolacrimal drainage system. RESULTS: The alpha-adrenergics caused a significant increase in the lumen width of the nasolacrimal drainage system, and the changes were more pronounced in the nasolacrimal duct than in the lacrimal sac. Although the nasolacrimal duct widening was more notable in the Alphagan-P(R) infusion group than the DL methylephedrine hydrochloride infusion group, there was no significant statistical difference. Patients' subjective symptoms improved in both groups. CONCLUSIONS: The alpha-adrenergics constrict the blood vessels of the cavernous body, leading to the increase in the lumen width of the nasolacrimal drainage system. This effect was more significant in the Alphagan-P(R) infusion group. In conclusion, infusion of alpha-adrenergics in patients with functional nasolacrimal duct obstruction can be considered as an alternative to surgical management.

The Effect of Brimonidine on Transepithelial Resistance in a Human Retinal Pigment Epithelial Cell Line

PURPOSE: To investigate the effects of brimonidine, an alpha-2-adrenergic agonist, on barrier function in ARPE-19 cells by measuring transepithelial resistance (TER). METHODS: ARPE-19 cells were cultured into a confluent monolayer on a microporous filter. Brimonidine was added to the apical medium, and the barrier function of the cells was evaluated by measuring TER. A subset of cells was treated under hypoxic conditions, and the TER changes observed upon administration of brimonidine were compared to those observed in cells in normoxic conditions. RESULTS: The ARPE cell membrane reached a peak resistance of 29.1+/-7.97 Omega cm2 after four weeks of culture. The TER of the cells treated under normoxic conditions increased with brimonidine treatment; however, the TER of the cells treated under hypoxic conditions did not change following the administration of brimonidine. CONCLUSIONS: Barrier function in ARPE-19 cells increased with brimonidine treatment. Understanding the exact mechanism of this barrier function change requires further investigation.

Intravenous dexmedetomidine prolongs bupivacaine spinal analgesia

The prolongation of spinal anesthesia by using clonidine through the oral, intravenous and spinal route has been known. The new ?2 agonist, dexmedetomidine has been proved to prolong the spinal anesthesia through the intrathecal route. We hypothesized that dexmedetomidine when administered intravenously following spinal block, also prolongs spinal analgesia. 48 patients were randomly allocated into two equal groups following receiving spinal isobaric bupivacaine 12.5 mg. Patients in group D received intravenously a loading dose of 1 microg/kg dexmedetomidine over 10 min and a maintenance dose of 0.5 microg/kg/hr. Patients in group C [the control group] received normal saline. The regression times to reach S1 sensory level and Bromage 0 motor scale, hemodynamic changes and the level of sedation were recorded. The duration of sensory block was longer in intravenous dexmedetomidine group compared with control group [261.5 +/- 34.8 min versus 165.2 +/- 31.5 min, P < 0.05]. The duration of motor block was longer in dexmedetomidine group than control group [199 +/- 42.8 min versus 138.4 +/- 31.3 min, P < 0.05]. Intravenous dexmedetomidine administration prolonged the sensory and motor blocks of bupivacaine spinal analgesia with good sedation effect and hemodynamic stability

Interaction of alpha[2]-adrenergic system and caffeine on passive avoidance learning in male Wistar rats

There are numerous studies on the effects of caffeine on memory and learning. The activation of alpha[2]-adrenoreceptors has been reported to impair memory functions in both rats and humans. In this study, interaction of alpha[2]-adrenergic system and caffeine on memory and learning was evaluated. In this experimental study, 90 wistar rats assigned into six groups of fifteen. Rats received yohimbine [4, 6, 8, 10 micro g]. The cannula was implanted into the right lateral ventricle of all rats with steriotaxi method. Then, they were trained in shuttlebox. Post-training intracerebroventricular [ICV] injection was carried out in all experiments and optimum doses were identified. Caffeine and yohimbine fostered memory and learning [p<0.001], while clonidine diminished these abilities compared to saline injection [p<0.05]. Co-administration of the optimum doses of clonidine and yohimbine showed statistically significant reduction in the time of step-through latency [p<0.05]. Instead, co-administration of clonidine and caffeine revealed no significant increase in the time of step-through latency [NS]. It is concluded that yohimbine and caffeine, unlike clonidine, increase memory

Alpha1 and alpha2 adrenoceptor mediated melanosome aggregatory responses in vitro in Oreochromis mossambica (Peters) melanophores.

Effects of specific and non-specific adrenoceptor agonists and antagonists were examined on the isolated scale melanophores of O. mossambica in physiological Ringer solution. The responses were recorded as melanophore size index. It was observed that adrenaline, nor-adrenaline, phenylpropanolamine, clonidine and phenylepherine induced melanosome aggregation in a dose-dependent manner. Denervation of the fish melanophores increased the sensitivity of the melanophores to adrenaline but not to nor-adrenaline. Phentolamine (3.55 x 10(-5) M), prazosin (2.38 x 10(-5) M) and yohimbine (2.821 x 10(-5) M) significantly inhibited the aggregatory responses of the fish melanophores to adrenaline, nor-adrenaline, clonidine and phenylepherine. The blocking effect of yohimbine was significantly higher than that of prazosin. It is concluded that the effect of adrenaline is directly mediated through the receptors and alpha2 adrenoceptors are predominantly involved in the aggregatory responses of this fish melanophores, while alpha1 adrenoceptors presence has been indicated.

Role of peripheral alpha2 adrenergic receptors in tonic pain during different stages of estrous cycle in rats

Estrogen and progesterone are supposed to modify pain sensitivity. However, the actual role of each of these steroid hormones in this respect is not well known. Plasma concentrations of these hormones show variation during estrous cycle. The role of alpha2 receptors in tonic pain has been pointed out. The aim of the present study was to investigate the agonist and antagonist effect of alpha2 adrenergic receptors on tonic pain sensitivity during all stages of estrous cycle in female rats. Xylasine as alpha 2 agonist and yohimbin as alpha 2 antagonist were used via intraperitoneal route [IP]. Adult rats weighing 180-200 grams were used. Animals were maintained on 12h reverse light/dark cycle for 7 days prior to the experiment. Water and food was available ad libitum. Formalin test was performed by subcutaneous injection of 50 micro l formalin [2.5%] solution into the hind paw. Formalin test was performed in all stages of estrous cycle for 60 minutes. Animals were divided into four groups; 1- control group [intact animal], 2- Sham group [animals received 0.2 ml normal saline by IP route], 3- Agonist groups [animals received 0.2 ml xylasine 1, 3 mg/kg body weight by IP route] and 4- Antagonist group [animals received 0.2 ml yohimbine 1, 3 mg/kg body weight by IP route]. Data were statistically analyzed using 2 way ANOVA test followed by Tukey's test as posthoc test. P < 0.05 was considered significant. Results showed that xylasine significantly [p < 0.05] decreases pain sensitivity in all stages of estrous cycle. Analgesic effect of xylasine was maximum in estrus stage of estrous cycle and minimum in metestrus stage of estrous cycle. Yohimbine significantly [p < 0.05] increases pain sensitivity in all stages of estrous cycle. Hyperalgesic effect of yohimbine was maximum in metestrus stage of estrous cycle and minimum in estrus stage of estrous cycle. These results indicate that alpha2 adrenergic system and endogenous steroids have an important role in pain sensitivity