PROPIVERINE HYDROCHLORIDE, AN ANTI-POLLAKIURIC AGENT, INHIBITS THE ACTIVITY OF ACTOMYOSIN ATPASE FROM THE URINARY-BLADDER

The present study was performed to investigate the effects of propiver ine hydrochloride (1-methyl-4-piperidyl diphenylpropoxyacetate hydroch loride, P-4), a novel anti-pollakiuric agent, on the contractile prote ins of smooth muscle. P-4 (30-300 mu M) inhibited the activity of nati ve actomyosin adenosine triphosphatase (ATPase) that had been freshly purified from canine urinary bladder, and calmodulin at 10 mu M overca me this inhibition. P-4 also inhibited myosin light chain kinase from smooth muscle in a dose-dependent manner. However, at 300 mu M, P-4 wa s unable to inhibit by 50% the activity of trypsin-treated myosin ligh t chain kinase, which was independent of Ca2+/calmodulin. 1 mol of cal modulin bound 4 to 5 mol of [C-14]P-4 in a Ca2+-dependent manner with a K-d of 77.4 mu M. These results indicate that calmodulin is one of t he intracellular target molecules for P-4 and that inhibition of the a ction of calmodulin by P-4 might cause the inhibition of actomyosin AT Pase activity, with subsequent relaxation of the smooth muscle of the urinary bladder. (C) 1997 Elsevier Science B.V.