[Effect of a muscarinic (M1) receptor agonist on sympathetic nerve activity in rats].
The present study was undertaken to elucidate the effect of novel muscarinic (M1) receptor agonist, AF102B, (+-)-cis-2-methyl-spiro(1,3-oxathiolane-5,3')-quinuclidine hydrochloride hemihydrate, on the sympatho-adrenomedullary function of anesthetized rats. Male Wistar rats were anesthetized intraperitoneally with urethane and alpha-chloralose. After immobilization with gallamine triethiodide, respiration was maintained artificially. Arterial blood pressure and heart rate were continuously monitored. Postganglionic inferior cardiac sympathetic nerve activity and preganglionic adrenal sympathetic nerve activity were recorded using an electrophysiological technique. In order to evaluate the adrenomedullary function, adrenal venous catecholamine secretion rate was also determined by HPLC-ECD method. Intravenous administration of AF102B (1 mg/kg, 10 mg/kg) produced a dose-dependent increase in cardiac sympathetic nerve activity that was accompanied with tachycardia both in nerve intact and pithed rats. AF102B produced a pressor effect in pithed rats but not in nerve intact rats. The AF102B-induced responses in pithed rats were significantly attenuated by the pretreatment with a M1 receptor selective antagonist, pirenzepine (50 micrograms/kg, i.v.). Moreover, AF102B produced a significant increase in adrenal epinephrine secretion rate without any increase in adrenal sympathetic nerve activity, which was also antagonized by pirenzepine pretreatment. These findings suggest that AF102B possesses an excitatory effect on the sympatho-adrenomedullary function which is mediated via pirenzepine sensitive muscarinic receptor of M1 subtype in anesthetized rats.
Saito
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First Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan.
D000313:Adrenal Medulla / Q000294:innervation; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D006321:Heart / Q000294:innervation; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D010277:Parasympathomimetics / Q000494:pharmacology*; D010890:Pirenzepine / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013876:Thiophenes
D010277:Parasympathomimetics; D011812:Quinuclidines; D011976:Receptors, Muscarinic; D013876:Thiophenes; D010890:Pirenzepine; C059240:cevimeline