Effects of endothelin on cytosolic Ca 2+ level and mechanical activity in rat uterine smooth muscle

Abstract

The effects of endothelin (ET) on cytosolic Ca 2+ level ([Ca 2+] i,) and mechanical activity were examined in isolated rat uterine smooth muscle. ET-1, ET-2, ET-3 and sarafotoxin S6b (STX) induced rhythmic contractions superimposed on an increased muscle tone. The concentration needed to induce a half-maximum contraction (EC 50) was 1.6–3.3 nM for ET-1. ET-2 and STX ind higher than 200 nM for ET-3, suggesting that the ET A receptor is responsible for these contractions. The sensitivity to ET-1 of uterus at day 20 of gestation was higher than that of non-pregnant rat uterus. Contraction induced by ET-1 followed an increase in [Ca 2+] i. The relation between [Ca 2+], and muscle tension, an indicator of Ca 2+ sensitivity of contractile elements, in :hc presence of ET-1 was identical to that in the presence of high K + in non-pregnant and pregnant rat uteri. The ET-i-induced increases in [Ca 2+] i, and muscle tension were strongly inhibited by verapamil in non-pregnant rat uterus. In pregnant rat uterus. however, verapamil only partially inhibited the increases. The verapamil-insensitive portions of [Ca 2+] i and contraction were inhibited by EGTA. In the absence of external Ca 2+ ET changed neither [Ca 2+], nor muscle tension. These results suggest that ET-1 acts on ET A receptors, increase [Ca 2+], and induces contraction without changing Ca 2+ sensitivity of contractile elements. The increase in [Ca 2 i], seemed to be mediated hy opening of L-type Ca 2+ channels in non-pregnant rat uterus and also of non-L-type Ca 2+ channels in pregnant rat uterus, hut not hy Ca 2+ release from intracellular storage sites.