The anticholinergic drug propiverine inhibits the protein kinase C activity in the rat urinary bladder.
There is ample evidence that non-cholinergic protein kinase C (PKC) mediated signal transduction pathways are involved into regulation of bladder smooth muscle contractions. To evaluate whether the anticholinergic and calcium modulating drug propiverine exerts intracellular effects by inhibition of the PKC, male inbred LEW 1A rats were pretreated with 0.6, 2, 6 and 60 mg/kg body weight for 5 days. Furthermore, competition assays with partially purified PKC were performed with propiverine in vitro. The activities of the membrane-bound and soluble PKC were assessed by 32P enrichment of lysine-rich histone.


RESULTS
The active, membrane-bound PKC decreased by about 60% accompanied by increase of the soluble form after propiverine in doses above 0.6 mg/kg. 100 nM of the drug inhibited the PKC also in vitro whereas the propiverine metabolites M5 and M6 and atropine were without any effect.


CONCLUSIONS
Propiverine was identified to be an inhibitor of the protein kinase C. Its contribution to the noncholinergic control of hyperactive detrusor smooth muscle cells needs further investigation.
Möritz
K U
KU
Department of Pharmacology, University of Greifswald, Germany.
Walter
R
R
May
K
K
Giessmann
T
T
Siegmund
W
W
D000818:Animals; D001561:Benzilates / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D004791:Enzyme Inhibitors; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects; D010276:Parasympatholytics / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D001743:Urinary Bladder / Q000187:drug effects / Q000201:enzymology* / Q000294:innervation
D001561:Benzilates; D004791:Enzyme Inhibitors; D010276:Parasympatholytics; C015586:propiverine; D011493:Protein Kinase C