Kazuhide Ayajiki (1), Tomio Okamura (1), Hideyuki Fujioka (1), Koichi
Nakayama (2), Kuniro Tsuji (3) and Noboru Toda (1)
(1) Department of Pharmacology, Shiga University of Medical Science,
Ohtsu 520-2192, Japan
Departments of (2) Pharmacology and (3) Biochemistry, School of Pharmaceutical
Sciences, University of Shizuoka, Shizuoka 422-8002, Japan
Abstract: 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 1O-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 NG-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.
Keywords: Nicotine, Neosurugatoxin, Nitric oxide-mediated nerve, Sensory
nerve, Duodenal ganglion