Prejunctional modulation of nitroxidergic nerve function in canine cerebral arteries.
Modulation by acetylcholine, VIP, clonidine, omega-conotoxin and Mg2+ of the relaxant response to electrical and chemical stimulation of nitroxidergic nerves, in which nitric oxide (NO) acts as a neurotransmitter, was investigated in isolated canine cerebral arteries. Acetylcholine attenuated the response, the inhibition being reversed by atropine; however, physostigmine failed to reduce the response. VIP in submaximal doses did not alter the neurally induced relaxation. The same was true with clonidine, morphine and naloxane. Treatment with omega-conotoxin depressed the response to electrical nerve stimulation but did not influence the nicotine-induced relaxation. Mg2+ inhibited the relaxation caused by nerve stimulation and Ca2+ reversed the response. It is concluded that activation of prejunctional muscarinic receptors seems to inhibit the synthesis of release of NO from nerve terminals but endogenous acetylcholine from cholinergic nerve does not play a role in inhibiting the nitroxidergic nerve function. Prejunctional VIP, alpha 2, adrenergic and opioid receptors are not likely to participate in the regulation of nerve function. Ca2+ responsible for NO synthase activation would be produced into nerve terminals via N-type Ca2+ channels when electrically stimulated and via non-N-, non-L-type channels when stimulated by nicotine. Mg2+ and Ca2+ counteract in the neurally induced relaxation, although the underlying mechanism was not determined.
Toda
N
N
Department of Pharmacology, Shiga University of Medical Sciences, Ohtsu, Japan.
Uchiyama
M
M
Okamura
T
T
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002536:Cerebral Arteries / Q000294:innervation*; D003000:Clonidine / Q000494:pharmacology; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D009538:Nicotine; D009569:Nitric Oxide / Q000502:physiology*; D010830:Physostigmine / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D009294:Narcotics; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; D009538:Nicotine; D009020:Morphine; D010830:Physostigmine; D008274:Magnesium; D003000:Clonidine; D000109:Acetylcholine; D002118:Calcium