Prejunctional regulation by endogenous and exogenous acetylcholine of adrenergic nerve function in isolated canine mesenteric arteries.
Transmural electrical stimulation (5-30 Hz) produced a frequency-dependent increase in the perfusion pressure of isolated, perfused dog mesenteric artery segments without the endothelium, which was abolished by prazosin or tetrodotoxin. Physostigmine inhibited the pressor response to transmural electrical stimulation, whereas atropine potentiated the response. Treatment with acetylcholine (10(-6) and 10(-5) M) dose-dependently inhibited the response to electrical nerve stimulation. The effect was reversed by the addition of atropine and AF-DX 116 at a concentration (10(-7) M) that selectively blocked the M2 receptor subtype, but not by pirenzepine or 4-DAMP. Acetylcholine did not alter the pressure raised by norepinephrine in perfused arterial segments nor the contraction caused by exogenous norepinephrine in the artery strips. 3H-overflow evoked by transmural electrical stimulation from tissues prelabeled with [3H] norepinephrine was decreased by acetylcholine (10(-6) M) in the superfused dog mesenteric arterial strips. It is concluded that acetylcholine inhibits adrenergic neurogenic contractions by interfering with the release of norepinephrine, which possibly results from activation of the prejunctional M2 receptor subtype.
Zhang
J X
JX
Department of Pharmacology, Shiga University of Medical Science, Seta, Japan.
Okamura
T
T
Toda
N
N
D000109:Acetylcholine / Q000494:pharmacology* / Q000502:physiology*; D000320:Adrenergic Fibers / Q000737:chemistry* / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D008297:Male; D008638:Mesenteric Arteries / Q000294:innervation*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D010830:Physostigmine / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D002800:Cholinesterase Inhibitors; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D014662:Vasoconstrictor Agents; D010890:Pirenzepine; D001285:Atropine; D010830:Physostigmine; D000109:Acetylcholine; D009638:Norepinephrine