EFFECTS OF CALMODULIN ANTAGONISTS ON TENSION AND CELLULAR CALCIUM CONTENT IN DEPOLARIZED VASCULAR AND INTESTINAL SMOOTH MUSCLES

Abstract

Several putative calmodulin antagonists have been examined for their inhibitory action on muscle tension and cellular Ca content in the K‐depolarized vascular and intestinal smooth muscles. The 65.4 mm K‐induced sustained contraction in the media‐intimal layer of rabbit aorta and the 45.4 mm K‐induced sustained contraction in guinea‐pig taenia coli were inhibited by the calmodulin antagonists, prenylamine, chlorpromazine, N2‐dansyl‐l‐argiiiine‐4‐t‐butylpiperadine amide (No. 233), and N‐(6‐aminohexyl)‐5‐chloro‐l‐naphthalenesulphonamide (W‐7), and also by the organic Ca antagonists, verapamil and diltiazem. The cellular Ca content in rabbit aorta and guinea‐pig taenia coli as measured by a modified lanthanum technique increased in the high‐K solutions. The increments were inhibited by these antagonists at concentrations similar to those required to inhibit the K‐induced contractions. However, W‐7 did not change (in aorta) or only slightly decreased (in taenia coli) the K‐induced increase in the cellular Ca content. A high concentration (2 × 10−4m) of W‐7 increased the resting cellular Ca content without increasing the muscle tension in aorta. The increment was inhibited by verapamil, sodium nitroprus‐side or hypoxia (N2 aeration). It is suggested that the inhibitory effects of prenylamine, chlorpromazine and No. 233 may be attributed mainly to the Ca antagonistic effect whereas W‐7 may inhibit the process beyond the transmembrane Ca influx. 1982 British Pharmacological Society