Functional studies on blockade by neosurugatoxin of nicotinic receptors in nitroxidergic and sensory nerve terminals and intramural ganglionic cells.
In isolated canine cerebral and cutaneous arteries and duodenum, effects of neosurugatoxin (NSTX) on the response to nicotine were compared. Nicotine-induced relaxations are mediated by nitric oxide (NO) from vasodilator nerves in cerebral arteries and by calcitonin gene-related peptide (CGRP) in cutaneous arteries treated with NO synthase inhibitors. Duodenal relaxation to nicotine is mediated by NO from inhibitory nerves. Cerebral arterial strips without endothelium responded to nicotine with relaxations that were inhibited by NSTX (3 x 10(-10) to 3 x 10(-9) M) concentration-dependently. Relaxations to nicotine of duodenal strips were attenuated by NSTX and abolished by tetrodotoxin, whereas those induced by K+ and electrical stimulation were not influenced. In cutaneous arteries treated with N(G)-nitro-L-arginine, nicotine-induced relaxations were attenuated by NSTX as low as 10(-10) M, but unaffected by tetrodotoxin. The inhibitory potency of NSTX was in the order of cutaneous artery > duodenum > cerebral artery. It is concluded that NSTX selectively antagonizes actions on nicotinic receptors in nitroxidergic nerves of cerebral arteries, CGRP-mediated sensory nerves of cutaneous artery and ganglionic cells of the duodenum, but the affinity of this toxin to nicotinic receptors in sensory nerves is the highest.
Ayajiki
K
K
Department of Pharmacology, Shiga University of Medical Science, Ohtsu, Japan.
Okamura
T
T
Fujioka
H
H
Nakayama
K
K
Tsuji
K
K
Toda
N
N
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002536:Cerebral Arteries / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005724:Ganglia / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008978:Mollusk Venoms / Q000494:pharmacology*; D009126:Muscle Relaxation / Q000187:drug effects; D009538:Nicotine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019335:Nitroarginine / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000502:physiology; D011978:Receptors, Nicotinic / Q000187:drug effects*; D012867:Skin / Q000098:blood supply / Q000187:drug effects / Q000294:innervation; D013779:Tetrodotoxin / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D008978:Mollusk Venoms; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D019335:Nitroarginine; D009569:Nitric Oxide; D013779:Tetrodotoxin; D009538:Nicotine; C036793:neosurugatoxin; D015740:Calcitonin Gene-Related Peptide