Role of oxotremorine in arginine vasopressin-induced hypothermia and its effects on behavioral thermoregulatory response in rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the role of oxotremorine in arginine vasopressin (AVP)-induced hypothermia and its effects on the behavioral thermoregulatory response.</p><p><b>METHODS</b>Core temperature (Tc), brown adipose tissue (BAT) temperature and motor activities were monitored in undisturbed female SD rats using radiotelemetry. The behavioral thermoregulatory response was monitored in rats using radiotelemetric temperature gradient apparatus. Effect of AVP (10 microg/kg) and oxotremorine (0.25 mg/kg) on Tc, motor activities, BAT temperature (T(BAT)), grooming activities and the behavioral thermoregulatory response were observed in rats.</p><p><b>RESULTS</b>Administration of AVP and oxotremorine caused a significant drop in Tc, T(BAT), and an increases in grooming activities, respectively. The hypothermic responses were accompanied with a preference for cooler ambient temperature. Oxotremorine augmented the reduction of Tc, T(BAT), and the elevation of grooming activities resulting from AVP, and lasting a longer time. Administration of oxotremorine followed immediately by AVP injection in rats was also shown to induce a preference for cooler ambient temperature, but there was no significant difference compared with AVP.</p><p><b>CONCLUSION</b>AVP-induced hypothermia was related with the set point temperature reduction, inhibiton of BAT thermogenesis and an increases in grooming activities. Oxotremorine could participate in peripheral AVP-induced hypothermia by affecting BAT thermogenesis and behavioral thermoregulation.</p>

La estimulación colinérgica central en la desnervación sinoaórtica. Efecto de la administración i.c.v. de agentes colinomiméticos / The central cholinergic stimulation in the sinoaortic denervation. Effect of the intracerebroventricular administration of cholinomimetic agents

Se decidió encarar el estudio farmacológico de la participación colinérgica en el modelo de desnervación sinoaórtica analizando los efectos cardiovasculares de agonistas muscarínicos diversos y del anticolinesterásico neostigmina administrados por vía endovenosa o por la vía intracerebroventricular. También se evaluó la actividad de la enzima acetilcolinesterasa en diversas estructras del sistema nervioso central luego de la a inhibición por administración intracerebral de neostigmina pero disminuye el efecto bradicardizante. Sin embargo no alteraría las respuestas cardiovasculares correspondientes a la inyección i.v. del agonista oxotremorina y a la i.c.v. del agonista McNeil-A-343. Luego de la administración i.c.v. de neostigmina, la actividad enzimática remanente osciló entre 24 por ciento a 30 por ciento en las estructuras hipotalámicas y entre 42 por ciento a 52 por ciento en los restantes tejidos, sin diferencias entre las ratas con operación simulada y aquellas con desnervación sinoaórtica. Los resultados sugieren que en los efectos cardiovasculares de la estimulación colinérgica central posiblemente no estarían involucrados receptores muscarínicos del subtipo M1. Por otra parte, no estaría afectada la degradación de la acetilcolina en el sistema nervioso central, lo que apoyaría la idea de un compromiso de receptores muscarínicos en los cambios observados. Por la ruta de administración utilizada de neostigmina, se observa un mayor grado de inhibición de la acetilcolinesterasa hipotalámica, sugiriendo entonces que las estructuras hipotalámicas podrían estar comprometidas en los efectos cardiovasculares inducidos por la administración intracerebral del anticolinesterásico.

Effect of K+-channel blockers on the muscarinic- and A|1-adenosine-receptor coupled regulation of electrically evoked acetylcholine release in the rat hippocampus

It was attempted to clarify the participation of K+ channels in the post-receptor mechanisms of the muscarinic and A1-adenosine receptor-mediated control of acetylcholine (ACh) release in the present study. Slices from the rat hippocampus were equilibrated with (3H)choline and the release of the labelled products was evoked by electrical stimulation (3 Hz, 5 V/cm, 2 ms, rectangular pulses), and the influence of various agents on the evoked tritium-outflow was investigated. Oxotremorine (Oxo, 0.1~10 micrometer), a muscarinic agonist, and N6-cyclopentyladenosine (CPA, 1~30 micrometer), a specific A1-adenosine agonist, decreased the ACh release in a dose-dependent manner, without affecting the basal rate of release. 4-aminopyridine (4AP), a specific A-type K+-channel blocker (1~100 micrometer), increased the evoked ACh release in a dose-related fashion, and the basal rate of release is increased by 3 and 100 micrometer. Tetraethylammonium (TEA), a non-specific K+-channel blocker (0.1~10 mM), increased the evoked ACh release in a dose-dependent manner without affecting the basal release. The effects of Oxo and CPA were not affected by 3 micrometer 4AP co-treatment, but 10 mM TEA significantly inhibited the effects of Oxo and CPA. 4AP (10 micrometer- and TEA (10 mM)-induced increments of evoked ACh release were completely abolished in Ca2+-free medium, but these were recovered in low Ca2+ medium. And the effects of K+-channel blockers in low Ca2+ medium were inhibited by Mg2+ (4 mM) and abolished by 0.3 micrometer tetrodotoxin (TTX). These results suggest that the changes in TEA-sensitive potassium channel permeability and the consequent limitation of Ca2+ influx are partly involved in the presynaptic modulation of the evoked ACh-release by muscarinic and A1-adenosine receptors of the rat hippocampus.

alpha-Adrenergic and cholinergic receptor agonists modulate voltage-gated Ca2+ channels

We investigated the effect of alpha-adrenergic and cholinergic receptor agonists on Ca2+ current in adult rat trigeminal ganglion neurons using whole-cell patch clamp methods. The application of acetylcholine, carbachol, and oxotremorine (50 muM each) produced a rapid and reversible reduction of the Ca2+ current by 17+/-6%, 19+/-3% and 18+/-4%, respectively. Atropine, a muscarinic antagonist, blocked carbachol-induced Ca2+ current inhibition to 3 +/- 1%. Norepinephrine (50 muM) reduced Ca2+ current by 18 +/- 2%, while clonidine (50 muM), an alpha2-adrenergic receptor agonist, inhibited Ca2+ current by only 4 +/- 1%. Yohimbine, an alpha2-adrenergic receptor antagonist, did not block the inhibitory effect of norepinephrine on Ca2+ current, whereas prazosin, an alpha1-adrenergic receptor antagonist, attenuated the inhibitory effect of norepinephrine on Ca2+ current to 6 +/- 1%. This pharmacology contrasts with alpha2-adrenergic receptor modulation of Ca2+ channels in rat sympathetic neurons, which is sensitive to clonidine and blocked by yohimbine. Our data suggest that the modulation of voltage dependent Ca2+ channel by norepinephrine is mediated via an alpha1-adrenergic receptor. Pretreatment with pertussis toxin (250 ng/ml) for 16 h greatly reduced norepinephrine- and carbachol-induced Ca2+ current inhibition from 17 +/- 3% and 18 +/- 3% to 2 +/- 1% and 2 +/- 1%, respectively. These results demonstrate that norepinephrine, through an alpha1-adrenergic receptor, and carbachol, through a muscarinic receptor, inhibit Ca2+ currents in adult rat trigeminal ganglion neurons via pertussis toxin sensitive GTP-binding proteins.