Yoshida M, Nishi K, Machida J, Sakiyama H, Ikeda K, Ueda S
Department of Urology, Kumamoto University School of Medicine, Japan.
Eur J Pharmacol. 1992 Nov 10;222(2-3):205-11. doi: 10.1016/0014-2999(92)90856-y.
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.
采用肌肉浴技术研究了佛波醇12,13 - 二丁酸酯（PDBu）对兔膀胱顶部和尿道的收缩作用。PDBu在两种组织中均引起浓度依赖性收缩，且这些反应不受阿托品、酚妥拉明、六甲铵或吲哚美辛预处理的影响。在两种组织中，蛋白激酶C（PKC）的强效抑制剂1 -（5 - 异喹啉基磺酰基）- 2 - 甲基哌嗪（H - 7）以浓度依赖性方式抑制PDBu诱导的收缩。膀胱顶部和尿道中PDBu诱导的最大收缩分别为氯化钾诱导的最大收缩的33.5±3.4%和33.3±4.1%。在无钙溶液中或用硝苯地平（10⁻⁶ M）预处理后，PDBu诱导的收缩减弱但未完全消除。虽然用PDBu（10⁻⁸ M）预处理对卡巴胆碱（在膀胱顶部）和去氧肾上腺素（在尿道）诱导的收缩反应没有显著影响，但用H - 7（100 μM）预处理对卡巴胆碱和去氧肾上腺素诱导的收缩有抑制作用；紧张相收缩比相性收缩更敏感。这些结果表明，PDBu在兔膀胱顶部和尿道中具有显著的收缩作用，且这些作用可能部分由PKC的激活介导。PKC的激活也可能有助于这些组织中激动剂诱导的收缩反应。
