Action Of Epinephrine Research Articles

Distinct phosphorylation sites/clusters in the carboxyl terminus regulate α1D-adrenergic receptor subcellular localization and signaling

The human α1D-adrenergic receptor is a seven transmembrane-domain protein that mediates many of the physiological actions of adrenaline and noradrenaline and participates in the development of hypertension and benign prostatic hyperplasia. We recently reported that different phosphorylation patterns control α1D-adrenergic receptor desensitization. However, to our knowledge, there is no data regarding the role(s) of this receptor's specific phosphorylation residues in its subcellular localization and signaling. In order to address this issue, we mutated the identified phosphorylated residues located on the third intracellular loop and carboxyl tail. In this way, we experimentally confirmed α1D-AR phosphorylation sites and identified, in the carboxyl tail, two groups of residues in close proximity to each other, as well as two individual residues in the proximal (T442) and distal (S543) regions. Our results indicate that phosphorylation of the distal cluster (T507, S515, S516 and S518) favors α1D-AR localization at the plasma membrane, i. e., substitution of these residues for non-phosphorylatable amino acids results in the intracellular localization of the receptors, whereas phospho-mimetic substitution allows plasma membrane localization. Moreover, we found that T442 phosphorylation is necessary for agonist- and phorbol ester-induced receptor colocalization with β-arrestins. Additionally, we observed that substitution of intracellular loop 3 phosphorylation sites for non-phosphorylatable amino acids resulted in sustained ERK1/2 activation; additional mutations in the phosphorylated residues in the carboxyl tail did not alter this pattern. In contrast, mobilization of intracellular calcium and receptor internalization appear to be controlled by the phosphorylation of both third-intracellular-loop and carboxyl terminus-domain residues. In summary, our data indicate that a) both the phosphorylation sites present in the third intracellular loop and in the carboxyl terminus participate in triggering calcium signaling and in turning-off α1D-AR-induced ERK activation; b) phosphorylation of the distal cluster appears to play a role in receptor's plasma membrane localization; and c) T442 appears to play a critical role in receptor phosphorylation and receptor-β-arrestin colocalization.

Different phosphorylation patterns regulate α1D-adrenoceptor signaling and desensitization

Human α1D-adrenoceptors (α1D-ARs) are a group of the seven transmembrane-spanning proteins that mediate many of the physiological and pathophysiological actions of adrenaline and noradrenaline. Although it is known that α1D-ARs are phosphoproteins, their specific phosphorylation sites and the kinases involved in their phosphorylation remain largely unknown. Using a combination of in silico analysis, mass spectrometry and site directed mutagenesis, we identified distinct α1D-AR phosphorylation patterns during noradrenaline- or phorbol ester-mediated desensitizations. We found that the G protein coupled receptor kinase, GRK2, and conventional protein kinases C isoforms α/β, phosphorylate α1D-AR during these processes. Furthermore, we showed that the phosphorylated residues are located in the receptor's third intracellular loop (S300, S323, T328, S331, S332, S334) and carboxyl region (S441, T442, T477, S486, S492, T507, S515, S516, S518, S543) and are conserved among orthologues but are not conserved among the other human α1-adrenoceptor subtypes. Additionally, we found that phosphorylation in either the third intracellular loop or carboxyl tail was sufficient to regulate calcium signaling desensitization. By contrast, mutations in either of these two domains significantly altered mitogen activated protein kinase (ERK) pathway and receptor internalization, suggesting that they have differential regulatory mechanisms. Our data provide new insights into the functional repercussions of these posttranslational modifications in signaling outcomes and desensitization.

The Beta 2 Adrenergic Receptor Antagonist Timolol Improves Healing of Combined Burn and Radiation Wounds.

In a scenario involving a nuclear detonation during war or a terrorist attack, acute radiation exposure combined with thermal and blast effects results in severe skin injury. Although the cutaneous injury in such a scenario may not be lethal, it may lead to inflammation, delayed wound healing and loss of the skin barrier, resulting in an increased risk of infection. In this study, we tested the potential use of timolol, a beta-adrenergic receptor antagonist, to improve epidermal wound closure after combined burn and radiation injury using an ex vivo human skin culture model. Daily application of 10 μ M timolol after combined injury (burn and 10 Gy ex vivo irradiation) increased wound epithelialization by 5-20%. In addition, exposure to 10 Gy significantly suppressed epidermal keratinocyte proliferation by 46% at 48 h postirradiation. Similar to what has been observed in a thermal burn injury, the enzyme phenylethanolamine N-methyltransferase (PNMT), which generates epinephrine, was elevated in the combined thermal burn and radiation wounds. This likely resulted in elevated tissue levels of this catecholamine, which has been shown to delay healing. Thus, with the addition of timolol to the wound to block the binding of locally generated epinephrine to the beta-adrenergic receptor, healing is improved. This work suggests that by antagonizing local epinephrine action within the wound, a beta-adrenergic receptor antagonist such as timolol may be a useful adjunctive treatment to improve healing in the combined burn and radiation injury.

Epinephrine Use during Newborn Resuscitation.

Epinephrine use in the delivery room for resuscitation of the newborn is associated with significant morbidity and mortality. Evidence for optimal dose, timing, and route of administration of epinephrine during neonatal resuscitation comes largely from extrapolated adult or animal literature. In this review, we provide the current recommendations for use of epinephrine during neonatal resuscitation and also the evidence behind these recommendations. In addition, we review the current proposed mechanism of action of epinephrine during neonatal resuscitation, review its adverse effects, and identify gaps in knowledge requiring urgent research.

Effect of resveratrol on platelet aggregation by fibrinogen protection

The effect of resveratrol (RSV) in inhibiting platelet adhesion and aggregation, as well as fibrinogen (FBG) conformational changes promoted by epinephrine (EP), were studied, by using complementary experimental techniques.NMR and IR spectroscopies were used to investigate possible protective effects by RSV towards FBG, in presence of EP. The protective effect of RSV towards FBG was highlighted by spin nuclear relaxation experiments that were interpreted for determining the thermodynamic equilibrium constants of FBG-EP interaction, and by infrared measurements, that showed EP-induced conformational changes of FBG.The ability of RSV in inhibiting platelet adhesion and aggregation promoted by EP was evaluated by scanning electron microscopy (SEM), measuring the platelet adhesion and aggregation degree, in comparison to data obtained for platelet aggregation in platelet rich plasma (PRP).The experimental combined approach pointed out that RSV is able to protect both FBG and platelets from the denaturant and aggregating action of EP at stress level concentration.

In vitro Research of the Concentration Dependence of Effect of Adrenaline on Platelets Aggregation.

Purpose. Paper intended to present experimental evidences that adrenaline has a direct effect of inducing platelets aggregation in the concentration range 1-8µM.Material/Methods. Platelet rich plasma from patients of Colentina Clinical Hospital, following an informed consent. The platelet rich plasma (PRP) was prepared by centrifuging the anticoagulated sample at 200 G for 10 minutes. Aggregation was evaluated by optical aggregometry, classical method of Born, using Helena PACKS-4 Aggregometer.Results. The curves transmission light-time followed the structure: a lag-time, a first phase aggregation, more or less linear, defined by a “Slope 1”, a second wave of aggregation defined by “slope 2” and a “saturation” phase. Slope 1 increases with the concentration of adrenaline. The second slopes of the aggregation curves, maximum aggregation and areas under curves depended linear on adrenaline concentration. Conclusions.Adrenaline, in concentrations in the 1-8µM, induce aggregation of human platelets from platelet rich plasma. Linear regression models for slope and area were practically identical suggesting a rather unique than biphasic mechanism of action of adrenaline during the time course of aggregation.

Endogenous α2A-Adrenoceptor-Operated Sympathoadrenergic Tones Attenuate Insulin Secretion via cAMP/TRPM2 Signaling.

In pancreatic β-cells, pharmacological concentrations of catecholamines, including adrenaline, have been used to inhibit insulin release and explore the multiple mechanisms involved. However, the significance of these signaling pathways for physiological adrenergic functions in β-cells is largely unknown. In the process of glucose-induced insulin secretion, opening of background current through nonselective cation channels (NSCCs) might facilitate membrane depolarization by closure of the ATP-sensitive K+ channels. Here, we examined whether physiological insulinostatic adrenaline action is mediated via the transient receptor potential melastatin 2 (TRPM2) channel, a type of NSCC, in β-cells. Results showed that physiological concentrations of adrenaline strongly suppressed glucose-induced and incretin-potentiated cAMP production and insulin secretion and inhibited NSCCs current and membrane excitability via the α2A-adrenoceptor in wild-type mice; however, insulin secretion was not attenuated in TRPM2-knockout (KO) mice. Administration of yohimbine, an α2-adrenoceptor antagonist, failed to affect glucose tolerance in TRPM2-KO mice, in contrast to an improved glucose tolerance in wild-type mice receiving the antagonist. The current study demonstrated that a physiological concentration of adrenaline attenuates insulin release via coupling of α2A-adrenoceptor to cAMP/TRPM2 signaling, thereby providing a potential therapeutic tool to treat patients with type 2 diabetes.

Epinephrine Vasoconstriction Effect Time in the Scalp Differs According to Injection Site and Concentration.

There have been few studies of the action of epinephrine injected into scalp tissue, or whether the action of epinephrine differs according to vascular anatomy within the same surgical field. Effective perioperative control of bleeding is critical during hair transplantation due to its time-consuming nature. To identify the vasoconstriction time of epinephrine by concentration and injection site in the scalp tissue. Twenty-five volunteers were injected with epinephrine at concentrations of 1:400,000, 1:200,000, 1:100,000, and 1:50,000 in the path of the supraorbital artery on the anterior hairline in the midfrontal area (Point A) and at the frontotemporal junction of the frontal hairline (Point B). Laser Doppler was used to measure scalp blood flow, and vasoconstriction time at Points A and B with each concentration of epinephrine was recorded. The duration of action of epinephrine increased in direct proportion with the concentration of epinephrine. The duration of vasoconstriction was shorter at Point A than at Point B, but this difference was only statistically significant at an epinephrine concentration of 1:50,000. The vasoconstriction time of epinephrine in the scalp correlated positively with concentration, and the duration of vasoconstriction was longer at Point B than at Point A.

Characterization of aromatic aminotransferases from Ephedra sinica Stapf.

Ephedra sinica Stapf (Ephedraceae) is a broom-like shrub cultivated in arid regions of China, Korea and Japan. This plant accumulates large amounts of the ephedrine alkaloids in its aerial tissues. These analogs of amphetamine mimic the actions of adrenaline and stimulate the sympathetic nervous system. While much is known about their pharmacological properties, the mechanisms by which they are synthesized remain largely unknown. A functional genomics platform was established to investigate their biosynthesis. Candidate enzymes were obtained from an expressed sequence tag collection based on similarity to characterized enzymes with similar functions. Two aromatic aminotransferases, EsAroAT1 and EsAroAT2, were characterized. The results of quantitative reverse transcription-polymerase chain reaction indicated that both genes are expressed in young stem tissue, where ephedrine alkaloids are synthesized, and in mature stem tissue. Nickel affinity-purified recombinant EsAroAT1 exhibited higher catalytic activity and was more homogeneous than EsAroAT2 as determined by size-exclusion chromatography. EsAroAT1 was highly active as a tyrosine aminotransferase with α-ketoglutarate followed by α-ketomethylthiobutyrate and very low activity with phenylpyruvate. In the reverse direction, catalytic efficiency was similar for the formation of all three aromatic amino acids using L-glutamate. Neither enzyme accepted putative intermediates in the ephedrine alkaloid biosynthetic pathway, S-phenylacetylcarbinol or 1-phenylpropane-1,2-dione, as substrates.

The use of α- or β-blockers to ameliorate the chronic stress of captivity in the house sparrow (Passer domesticus).

When wild animals are brought into captivity for the first time, they frequently develop chronic stress symptoms. Animals can develop glucocorticoid dysregulation or changes in the sympathetic nervous system over the course of the first week in captivity. By blocking the action of epinephrine and norepinephrine using α- or β-blockers, we hoped to reduce the degree of chronic stress symptoms exhibited by newly captured house sparrows. We measured corticosterone, heart rate and heart rate variability in 24 house sparrows (Passer domesticus) over the first week of captivity. The birds were treated with saline, propranolol (a β-blocker) or phentolamine (an α-blocker) for the first 3days of captivity. We also compared newly captured animals with animals that had been held in captivity for 1month. During the first week of captivity, baseline corticosterone increased, but that increase was blocked by propranolol. Heart rate was not different between the treatment groups, but it was higher during the first week than after 1month in captivity. Sympathetic nervous system activity (as measured by heart rate variability) decreased over the first week of captivity, but was not affected by treatment. β-Blockers, but not α-blockers, might help to improve some symptoms of chronic stress in newly captured animals.

Short-term effect of adrenalin on S-100b and N-CAM level in the different rat brain areas

The level of adrenalin grows under stress conditions, sense of danger, anxiety, fear, trauma, burns and shock. In high concentrations adrenaline increases the speed of protein catabolism. Working through the circulatory system, adrenaline affects almost all the functions of organs, causing the body mobilization to counter stressful situations. Due to ELISA the astrocytes-specific protein (S-100b) and neural cell adhesion molecule (N-CAM) were studied. S-100b is produced mainly by astrocytes іn the brain and depending on the concentration it causes trophic or toxic effect on the neurons and glial cells.Strong stress and ischemia induce re-distribution of calcium-binding protein S-100b and elevation of its level. Quantitative changes of S-100b under the influence of various factors on the body which lead to the metabolic disorder in the brain are considered today as a sign of brain damage (cortical, ischemic one, etc.). Fluctuations in the concentration of S-100b in the brain are not always accompanied by marked deterioration of the physical condition of animals, but they can also lead to a number of violations of integrative functions of the brain depending on over-production of this protein. Most N-CAM are transmembrane proteins that cross the plasma membraneonce; intracellular domains have different size and it is thought they are involved in binding to cytoskeleton or cell signaling. Violation of N-CAM functions leads to disruption of nerve sprouts. Data obtained in our study showed no serious re-distribution of S-100b and N-CAM level in the different areas of rat brain (cerebral cortex, hippocampus and thalamus) under effect of adrenalin administered to the animals (under skin) in dosage of 0.45–0.60 mg per rat, 1 time per day during 10 days, probably because of the type of injection and/or short time of adrenalin action. Increased dosage of adrenaline 1 hour before decapitation leads to the decrease of level of total protein in membrane fraction extracted from brain tissue without changing the level of S-100b and N-CAM.

From cocaine to lidocaine

From cocaine to lidocaine

Convergent evolution of neural systems in ctenophores.

Neurons are defined as polarized secretory cells specializing in directional propagation of electrical signals leading to the release of extracellular messengers - features that enable them to transmit information, primarily chemical in nature, beyond their immediate neighbors without affecting all intervening cells en route. Multiple origins of neurons and synapses from different classes of ancestral secretory cells might have occurred more than once during ~600 million years of animal evolution with independent events of nervous system centralization from a common bilaterian/cnidarian ancestor without the bona fide central nervous system. Ctenophores, or comb jellies, represent an example of extensive parallel evolution in neural systems. First, recent genome analyses place ctenophores as a sister group to other animals. Second, ctenophores have a smaller complement of pan-animal genes controlling canonical neurogenic, synaptic, muscle and immune systems, and developmental pathways than most other metazoans. However, comb jellies are carnivorous marine animals with a complex neuromuscular organization and sophisticated patterns of behavior. To sustain these functions, they have evolved a number of unique molecular innovations supporting the hypothesis of massive homoplasies in the organization of integrative and locomotory systems. Third, many bilaterian/cnidarian neuron-specific genes and 'classical' neurotransmitter pathways are either absent or, if present, not expressed in ctenophore neurons (e.g. the bilaterian/cnidarian neurotransmitter, γ-amino butyric acid or GABA, is localized in muscles and presumed bilaterian neuron-specific RNA-binding protein Elav is found in non-neuronal cells). Finally, metabolomic and pharmacological data failed to detect either the presence or any physiological action of serotonin, dopamine, noradrenaline, adrenaline, octopamine, acetylcholine or histamine - consistent with the hypothesis that ctenophore neural systems evolved independently from those in other animals. Glutamate and a diverse range of secretory peptides are first candidates for ctenophore neurotransmitters. Nevertheless, it is expected that other classes of signal and neurogenic molecules would be discovered in ctenophores as the next step to decipher one of the most distinct types of neural organization in the animal kingdom.

Epinephrine-stimulated glycogen breakdown activates glycogen synthase and increases insulin-stimulated glucose uptake in epitrochlearis muscles.

Epinephrine increases glycogen synthase (GS) phosphorylation and decreases GS activity but also stimulates glycogen breakdown, and low glycogen content normally activates GS. To test the hypothesis that glycogen content directly regulates GS phosphorylation, glycogen breakdown was stimulated in condition with decreased GS activation. Saline or epinephrine (0.02 mg/100 g rat) was injected subcutaneously in Wistar rats (∼130 g) with low (24-h-fasted), normal (normal diet), and high glycogen content (fasted-refed), and epitrochlearis muscles were removed after 3 h and incubated ex vivo, eliminating epinephrine action. Epinephrine injection reduced glycogen content in epitrochlearis muscles with high (120.7 ± 17.8 vs. 204.6 ± 14.5 mmol/kg, P < 0.01) and normal glycogen (89.5 ± 7.6 vs. 152 ± 8.1 mmol/kg, P < 0.01), but not significantly in muscles with low glycogen (90.0 ± 5.0 vs. 102.8 ± 7.8 mmol/kg, P = 0.17). In saline-injected rats, GS phosphorylation at sites 2+2a, 3a+3b, and 1b was higher and GS activity lower in muscles with high compared with low glycogen. GS sites 2+2a and 3a+3b phosphorylation decreased and GS activity increased in muscles where epinephrine decreased glycogen content; these parameters were unchanged in epitrochlearis from fasted rats where epinephrine injection did not decrease glycogen content. Incubation with insulin decreased GS site 3a+3b phosphorylation independently of glycogen content. Insulin-stimulated glucose uptake was increased in muscles where epinephrine injection decreased glycogen content. In conclusion, epinephrine stimulates glycogenolysis in epitrochlearis muscles with normal and high, but not low, glycogen content. Epinephrine-stimulated glycogenolysis decreased GS phosphorylation and increased GS activity. These data for the first time document direct regulation of GS phosphorylation by glycogen content.

Abstract 148: Zoniporide Combined with α-Methylnorepinephrine Appears Highly Effective for Resuscitation from Cardiac Arrest in a Rat Model of Ventricular Fibrillation

Background: We have reported in rat and swine models of cardiac arrest that sodium hydrogen exchanger isoform-1 (NHE-1) inhibition facilitates resuscitation, ameliorates myocardial dysfunction, and improves survival. Others have reported that α-methylnorepinephrine (α-MNE) - a selective α2-adrenoreceptor agonist - is superior to epinephrine given its lack of β-agonist effects. We examined in a rat model of VF and closed-chest resuscitation the effects of combining the NHE-1 inhibitor zoniporide (ZNP) with α-MNE. Methods: VF was electrically induced in 32 male retired breeder Sprague-Dawley rats and left untreated for 8 minutes after which resuscitation was attempted by an 8 minute interval of chest compression and delivery of electrical shocks. Rats were randomized 1:1:1:1 to receive a 3 mg/kg bolus of ZNP or 0.9% NaCl before starting chest compression and a 100 μg/kg bolus of α-MNE or its vehicle at minute 2 of chest-compressions establishing 4 groups of 8 rats each. Successfully resuscitated rats were monitored for 240 minutes. Results: The number of rats that had return of spontaneous circulation and then survived 240 min were: α-MNE(-)/ZNP(-) 4 and 2; α-MNE(-)/ZNP(+) 5 and 5; α-MNE(+)/ZNP(-) 2 and 1; and α-MNE(+)/ZNP(+) 7 and 7 yielding a statistically significant effect on overall survival times corresponding to 105 ± 114, 150 ± 124, 58 ± 108, and 210 ± 85 min, respectively (p &lt; 0.045). Post-resuscitation lactate levels were attenuated in all treatment groups with the greatest effect by the α-MNE(+)/ZNP(+) combination without major differences in hemodynamic function (Table). Conclusion: We confirm a beneficial effect resulting from the combination of ZNP (given to attenuate myocardial reperfusion injury) and α-MNE (given to augment peripheral vascular resistance during chest compression without the detrimental actions of epinephrine). The proposed combination may prove to be a highly effective novel strategy for resuscitation from cardiac arrest.

Adrenergic control of lipolysis in women compared with men.

Data suggest women are more sensitive to the lipolytic action of epinephrine compared with men while maintaining similar glucoregulatory effects (Horton et al. J Appl Physiol 107: 200-210, 2009). This study aimed to determine the specific adrenergic receptor(s) that may mediate these sex differences. Lean women (n = 14) and men (n = 16) were studied on 4 nonconsecutive days during the following treatment infusions: saline (S: control), epinephrine [E: mixed β-adrenergic (lipolytic) and α2-adrenergic (antilipolytic) stimulation], epinephrine + phentolamine (E + P: mixed β-adrenergic stimulation only), and terbutaline (T: selective β2-adrenergic stimulation). Tracer infusions of glycerol, palmitate, and glucose were administered to determine systemic lipolysis, free fatty acid (FFA) release, and glucose turnover, respectively. Following basal measurements, substrate and hormone concentrations were measured in all subjects over 90 min of treatment and tracer infusion. Women had greater increases in glycerol and FFA concentrations with all three hormone infusions compared with men (P < 0.01). Glycerol and palmitate rate of appearance (Ra) and rate of disappearance (Rd) per kilogram body weight were greater with E infusion in women compared with men (P < 0.05), whereas no sex differences were observed with other treatments. Glucose concentration and kinetics were not different between sexes with any infusion. In conclusion, these data support the hypothesis that the greater rate of lipolysis in women with infusion of E was likely due to lesser α2 antilipolytic activation. These findings may help explain why women have greater lipolysis and fat oxidation during exercise, a time when epinephrine concentration is elevated.

Auto-injector needle length may be inadequate to deliver epinephrine intramuscularly in women with confirmed food allergy.

BackgroundEpinephrine auto-injectors are the standard first aid treatment for anaphylaxis. Intramuscular delivery into the anterolateral aspect of the thigh is recommended for optimal onset of action of epinephrine. The most frequently prescribed auto-injector in North America and Canada is the EpiPen®, which has a needle length of 15.2 mm. Currently, it is unknown whether this needle length is adequate for intramuscular delivery of epinephrine in adult patients at risk of anaphylaxis.MethodsOne hundred consecutive adult patients with confirmed food allergy requiring an epinephrine auto-injector were recruited. Skin to muscle depth (STMD) at the right mid-anterolateral thigh was measured using ultrasound under minimal (min) and maximum (max) pressure. The EpiPen® needle length was considered adequate if STMDmax was ≤15.2 mm. Baseline characteristics including age, gender, ethnicity, and body mass index (BMI) were compared in patients with STMDmax ≤15.2 mm vs. >15.2 mm.ResultsThe EpiPen® needle length of 15.2 mm was inadequate for intramuscular delivery in 19 of the 100 enrolled patients (19%), all of whom were female; 28% of women had a STMDmax >15.2 mm. The mean STMDmax in the ≤15.2-mm and >15.2-mm groups were 9 ± 4 mm and 20 ± 4 mm, respectively (p = 0.0001). Linear regression analysis found BMI to be significantly associated with STMDmax after adjusting for age (p < 0.001).ConclusionsThe needle length of the epinephrine auto-injectors may not be adequate for intramuscular delivery of epinephrine in a large proportion of women with food allergy; this may impact morbidity and mortality from anaphylaxis in this patient population.

Function and expression of sulfonylurea, adrenergic, and glucagon-like peptide 1 receptors in isolated porcine islets.

The scarcity of human cadaveric pancreata limits large-scale application of islet transplantation for patients with diabetes. Islets isolated from pathogen-free pigs provide an economical and abundant alternative source assuming immunologic barriers are appropriate. Membrane receptors involved in insulin secretion that also have potential as imaging targets were investigated in isolated porcine islets. Quantitative (q)PCR revealed that porcine islets express mRNA transcripts for sulfonylurea receptor 1 (Sur1), inward rectifying potassium channel (Kir6.2, associated with Sur1), glucagon-like peptide 1 receptor (GLP1R), and adrenergic receptor alpha 2A (ADRα2A). Receptor function was assessed in static incubations with stimulatory glucose concentrations, and in the presence of receptor agonists. Glibenclamide, an anti-diabetic sulfonylurea, and exendin-4, a GLP-1 mimetic, potentiated glucose-stimulated insulin secretion >2-fold. Conversely, epinephrine maximally reduced insulin secretion 72 ± 9% (P < 0.05) and had a half maximal inhibitory concentration of 60 nm in porcine islets (95% confidence interval of 45-830 nm). The epinephrine action was inhibited by the ADRα2A antagonist yohimbine. Our findings demonstrate that porcine islets express and are responsive to both stimulatory and inhibitory membrane localized receptors, which can be used as imaging targets after transplantation or to modify insulin secretion.

Imidazoline use in sinonasal surgery

The nasal mucosa is very vascular, receiving more blood flow per cubic centimeter of tissue than does muscle, brain or liver (Drettner and Aust, 1974; [1]). This vascularity can present a major problem during sinus surgery. Surgeons routinely use topical vasoconstrictors in endoscopic sinus surgery however, the optimal regimen is not clear. Imidazoline nasal sprays are often used up to 1hour before sinonasal surgery to aid in intraoperative vasoconstriction. After the induction of anaesthesia, epinephrine-based topical and submucosal preparations are subsequently administered to further enhance vasoconstriction. Imidazolines are non-selective, partial alpha adrenoceptor agonists with a higher affinity, yet lower potency, for alpha adrenoceptors when compared to epinephrine. It is hypothesized that imidazolines block the action of epinephrine on the alpha adrenoceptors of the nasal mucosa resulting in less vasoconstriction, and a poorer intra-operative field, when compared to the use of epinephrine alone. This paper hypothesizes that preoperative imidazoline administration may adversely affect optimal intra-operative vasoconstriction.

Участь ейкозаноїдів у механізмі скоротливих реакцій ворітної вени на дію адреналіну і норадреналіну

The influence of indometacine (7 x 10(-8)M) on the tonic contractile activity of the isolated rat portal vein (PV) under the action of adrenaline (1 x 10(-5)M) and noradrenaline (5 x 10(-6)M) was studied. Indometacine decreased the amplitude of noradrenaline-induced tonic constriction of PV with intact endothelium and produced no effect on constriction of vessels with denuded endothelial layer. The results suggest that these reactions are mediated by endothelial prostanoids. Inhibition of adrenaline-induced constriction of PV preparations with intact and denuded endothelium suggests that the contractile reactions are mediated by prostanoides derived from both endothelial and smooth muscle cells.