Effects of phorbol ester on lower urinary tract smooth muscles in rabbits

The contractile effects of phorbol 12,13-dibutyrate (PDBu) on rabbit urinary bladder dome and urethra were investigated using muscle bath techniques. PDBu caused concentration-dependent contractions in both tissues, and these responses were not affected by pretreatment with atropine, phentolamine, hexamethonium or indomethacin. In both tissues, 1-(5-isoquinolinyl-sulfonyl)-2-methylpiperazine (H-7), a potent inhibitor of protein kinase C (PKC), inhibited PDBu-induced contractions in a concentration-dependent manner. The maximum PDBu-induced contractions in bladder dome and urethra were 33.5 +/- 3.4 and 33.3 +/- 4.1% of KCl-induced maximum contractions, respectively. In Ca(2+)-free solution or after pretreatment with nifedipine (10(-6) M), PDBu-induced contractions were reduced but not completely abolished. Although pretreatment with PDBu (10(-8) M) did not have a significant effect on the contractile responses induced by carbachol (in bladder dome) and phenylephrine (in urethra), pretreatment with H-7 (100 microM) had an inhibitory effect on carbachol- and phenylephrine-induced contractions; tonic phase contractions were more sensitive than phasic contractions. These results indicate that PDBu has significant contractile effects in rabbit bladder dome and urethra, and that the effects may be partly mediated by activation of PKC. PKC activation might also contribute to agonist-induced contractile responses in these tissues.