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 μM) inhibited the activity of native actomyosin adenosine triphosphatase (ATPase) that had been freshly purified from canine urinary bladder, and calmodulin at 10 μM overcame this inhibition. P-4 also inhibited myosin light chain kinase from smooth muscle in a dose-dependent manner. However, at 300 μM, P-4 was unable to inhibit by 50% the activity of trypsin-treated myosin light chain kinase, which was independent of Ca 2+/calmodulin. 1 mol of calmodulin bound 4 to 5 mol of [ 4 C ]P-4 in a Ca 2+-dependent manner with a K d of 77.4 μM. 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.
Published Version
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