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, effec ts of neosurugatoxin (NSTX) on the response to nicotine were compared. Nicotine-induced relaxations are mediated by nitric oxide (NO) from v asodilator nerves in cerebral arteries and by calcitonin gene-related peptide (CGRP) in cutaneous arteries treated with NO synthase inhibito rs. Duodenal relaxation to nicotine is mediated by NO from inhibitory nerves. Cerebral arterial strips without endothelium responded to nico tine with relaxations that were inhibited by NSTX (3 x 10(-10) to 3 x 10(-9) M) concentration-dependently. Relaxations to nicotine of duoden al strips were attenuated by NSTX and abolished by tetrodotoxin, where as those induced by Ki and electrical stimulation were not influenced. In cutaneous arteries treated with NG-nitro-L-arginine, nicotine-indu ced relaxations were attenuated by NSTX as low as 10(-10) M, but unaff ected by tetrodotoxin. The inhibitory potency of NSTX was in the order of cutaneous artery > duodenum > cerebral artery. It is concluded tha t NSTX selectively antagonizes actions on nicotinic receptors in nitro xidergic nerves of cerebral arteries, CGRP-mediated sensory nerves of cutaneous artery and ganglionic cells of the duodenum, but the affinit y of this toxin to nicotinic receptors in sensory nerves is the highes t.