Effect of ?-conotoxin on cholinergic and tachykininergic excitatory neurotransmission to the circular muscle of the guinea-pig colon

Abstract

The aim of this study was to compare the stimulus-response characteristics of the cholinergic and tachykininergic excitatory transmission to the circular muscle of the guinea-pig proximal colon and their susceptibility to inhibition by the N-type calcium channel blocker omega-conotoxin (CTX). All experiments were performed in the presence of guanethidine (3 microM), indomethacin (10 microM), L-nitroarginine (L-NOARG, 30 microM) and apamin (0.1 microM). In the presence of the tachykinin receptor antagonists, FK 888 (10 microM0 and GR 94,800 (3 microM), to block NK1 and NK2 receptors, respectively, electrical field stimulation (EFS) produced frequency-dependent atropine- (1 microM) sensitive contractions. In the presence of atropine (1 microM), EFS produced tachykininergic contractions which were abolished by the combined administration of FK 888 (10 microM) and GR 94,800 (3 microM). The maximal responses produced by cholinergic and tachykininergic neurotransmission ranged between 80 and 100% of the maximal contractile response to 80 mM KCl. The frequency of stimulation, pulse width and voltage required to produce 50% of the maximal cholinergic and tachykininergic contraction were not different from each other, although cholinergic transmission appeared more efficient in producing twitch contractions in response to single pulse EFS. Furthermore, cholinergic transmission was more efficient than tachykininergic transmission in producing contraction in response to short periods of EFS. CTX (0.1 microM for 30 min) produced a large and comparable rightward shift of the cholinergic and tachykininergic frequency-response curve (19 and 17 fold increase in the frequency of stimulation producing 50% of the maximal response, respectively) and markedly depressed (51 and 43% inhibition, respectively) the maximal concentrations response.(ABSTRACT TRUNCATED AT 250 WORDS)