The effect of omega conotoxin GVIA, a peptide modulator of the N-type voltage sensitive calcium channels, on motor responses produced by activation of efferent and sensory nerves in mammalian smooth muscle

Abstract

1. The effect of omega-conotoxin (CTX) GVIA, a peptide which blocks neuronal calcium channels, were investigated on nerve-mediated motor responses in a variety of isolated smooth muscle preparations from rats and guinea-pigs. 2. In the rat or guinea-pig isolated vas deferens CTX (1 nM-1 microM) produced a concentration and time-related inhibition of the response to field stimulation, while the responses to KCl, noradrenaline or adenosine triphosphate were unaffected. In the presence of CTX a series of tetrodotoxin-resistant contractions could be elicited by field stimulation by increasing pulse width and/or voltage. 3. In the rat or guinea-pig isolated urinary bladder, CTX produced a concentration and time-dependent inhibition of twitch responses to field stimulation without affecting the response to exogenous acetylcholine. In the rat bladder the maximal effect did not exceed 25% inhibition while a much larger fraction of the response (about 70%) was inhibited in the guinea-pig bladder. The CTX-resistant response was abolished, in both tissues, by tetrodotoxin. 4. The effects of CTX in the rat bladder were also studied with a whole range of frequencies of field stimulation (0.1-50 Hz). Maximal inhibition was observed toward contractions elicited at frequencies of 2-5 Hz. At low frequencies the inhibitory effects of CTX and atropine were almost additive while at high frequencies of stimulation a large component of the atropine-sensitive response was CTX-resistant. 5. In the rat isolated proximal duodenum, field stimulation in the presence of atropine and guanethidine produced a primary relaxation followed by a rebound contraction.(ABSTRACT TRUNCATED AT 250 WORDS)