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tPropiverine Hydrochloride, Anti-Pollakiuric Agent, inhibits the Activity of Actomyosin ATPase from the Urinary Bladder.
1997/08/20
Matsushima S, Inada H, Asai T, Naka M, Tanaka T.
Eur J Pharmacol. 1997 Aug 20;333(1):93-7
Abstract
The present study was performed to investigate the effects of propiverine hydrochloride (1-methyl-4-piperidyl diphenylpropoxyacetate hydrochloride, P-4), a novel anti-pollakiuric agent, on the contractile proteins of smooth muscle. P-4 (30-300 microM) inhibited the activity of native actomyosin adenosine triphosphatase (ATPase) that had been freshly purified from canine urinary bladder, and calmodulin at 10 microM overcame this inhibition. P-4 also inhibited myosin light chain kinase from smooth muscle in a dose-dependent manner. However, at 300 microM, P-4 was unable to inhibit by 50% the activity of trypsin-treated myosin light chain kinase, which was independent of Ca2+/calmodulin. 1 mol of calmodulin bound 4 to 5 mol of [14C]P-4 in a Ca2+-dependent manner with a K(d) of 77.4 microM. These results indicate that calmodulin is one of the intracellular target molecules for P-4 and that inhibition of the action of calmodulin by P-4 might cause the inhibition of actomyosin ATPase activity, with subsequent relaxation of the smooth muscle of the urinary bladder.