Abstract

We have determined the response of two types of rat gastric smooth muscle to the cumulative addition of endothelin-1 (ET-1). Both the longitudinal smooth muscle (tonic) from the forestomach and the circular smooth muscle (phasic) from the fundus were used in this study. Longitudinal smooth muscle contracted in a concentration-dependent manner in response to ET-1. The ET-1-induced contractions were abolished by the use of either nifedipine or calcium-free solutions. The maximal stress developed was 1.13 +/- 0.12 x 10(5) N/m2, or about 61% of the maximal carbachol response in this tissue. The EC50 for the ET-1-induced contraction was 11.4 +/- 2.3 nM. In contrast to the contractile effect on longitudinal smooth muscle, ET-1 produced a potent concentration-dependent inhibition of both the spontaneous phasic activity and carbachol-stimulated activity of the circular smooth muscle. The maximal inhibitory effect in response to ET-1 occurred at about 10 nM. The abolition of phasic activity lasted about 15 minutes before phasic activity returned. ET-1 also inhibited carbachol-induced increases in the phasic activity of circular smooth muscle with a similar potency. Inhibitors of arachidonic acid products, indomethacin or nordihydroguaiaretic acid, did not affect the response to ET-1 of either longitudinal or circular smooth muscle. Similarly, inhibition of nitric oxide, vasoactive intestinal peptide (VIP) calcitonin-related peptide (CGRP) and inhibition of endogenous neural pathways by tetrodotoxin (TTX), atropine, hexamethonium, cold storage or phentolamine did not reverse the inhibitory response of the circular smooth muscle to ET-1.(ABSTRACT TRUNCATED AT 250 WORDS)