Effects of semotiadil fumarate, a novel Ca2+ antagonist, on cytosolic Ca2+ level and force of contraction in porcine coronary arteries.

Abstract:

:1. The mechanisms of action of semotiadil fumarate, a novel Ca2+ antagonist, were examined by measuring the cytosolic Ca2+ level ([Ca2+]i) and force of contraction in porcine coronary arteries, and by determining [3H]-pyrilamine binding to bovine cerebellar membranes. 2. Semotiadil or verapamil (0.1 and 1 microM) inhibited both the high KCl-induced increases in [Ca2+]i and force in a concentration-dependent manner. 3. Histamine (30 microM) produced transient increases followed by sustained increases in [Ca2+]i and force, which were inhibited by semotiadil and verapamil (1 and 10 microM). The agents were different in that semotiadil reduced the maximum [Ca2+]i and force responses to histamine, but not pD2 values, whereas verapamil did reduce the pD2 values for histamine, but not the maximum responses. 4. Verapamil (10 microM), but not semotiadil, inhibited histamine-induced increases in [Ca2+]i and force in Ca(2+)-free solution. Neither semotiadil nor verapamil affected the increases in [Ca2+]i and force induced by caffeine. Semotiadil even at the higher concentration (10 microM) did not displace specific binding of [3H]-pyrilamine to bovine cerebellar membranes. 5. These results suggest that semotiadil inhibits both KCl- and histamine-induced contractions mainly by blocking voltage-dependent L-type Ca2+ channels.

journal_name

Br J Pharmacol

authors

Kageyama M,Yanagisawa T,Taira N

doi

10.1111/j.1476-5381.1995.tb13345.x

subject

Has Abstract

pub_date

1995-03-01 00:00:00

pages

1289-95

issue

6

eissn

0007-1188

issn

1476-5381

journal_volume

114

pub_type

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