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 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.
Matsushima
S
S
Department of Molecular and Cellular Pharmacology, Mie University School of Medicine, Tsu, Japan.
Inada
H
H
Asai
T
T
Naka
M
M
Tanaka
T
T
D000818:Animals; D001561:Benzilates / Q000378:metabolism / Q000494:pharmacology*; D002147:Calmodulin / Q000378:metabolism; D002417:Cattle; D003285:Contractile Proteins / Q000378:metabolism; D003956:Dialysis; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D009130:Muscle, Smooth / Q000378:metabolism; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism; D009218:Myosins / Q000037:antagonists & inhibitors*; D011485:Protein Binding; D001743:Urinary Bladder / Q000187:drug effects / Q000201:enzymology*
D001561:Benzilates; D002147:Calmodulin; D003285:Contractile Proteins; D004791:Enzyme Inhibitors; C015586:propiverine; D009219:Myosin-Light-Chain Kinase; D009218:Myosins