Department of Pharmacology, School of Medicine, University of Cukurova, Adana, Turkey.
J Pharmacol Exp Ther. 2010 Apr;333(1):228-35. doi: 10.1124/jpet.109.161661. Epub 2010 Jan 5.
The present study was undertaken to compare the effects of the thiol reagents L-cysteine and (diazene dicarboxylic acid bis 5N,N-dimethylamide) diamide on contractile activity of neonatal and adult rat bladders. In vitro whole-bladder preparations from Wistar rats were used to study the modulation of spontaneous bladder contractions by thiol reagents. After blocking cholinergic and adrenergic transmission with atropine and guanethidine, L-cysteine facilitated spontaneous bladder contractions in neonatal rat bladders. The effect of L-cysteine was suppressed by diamide. Diamide alone did not change basal activity of the neonatal rat bladder. The facilitatory effects of L-cysteine were reduced by the L-type Ca2+ channel-blocking agent nifedipine and the calcium-activated K+ channel opener NS1619 [1,3-dihydro-1-[2-hydroxy-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-2H-benzimidazol-2-one]. ATP or suramin, a purinergic receptor antagonist, significantly inhibited the effect of L-cysteine in neonatal bladders, whereas the nitric-oxide synthase inhibitor N(omega)-nitro-L-arginine was ineffective. L-cysteine did not elicit any detectable effects in the adult rat bladder; whereas diamide caused a large-amplitude sustained tonic contraction. The contraction induced by diamide in adult bladder did not occur when the preparation was pretreated with L-cysteine. Also, L-Cysteine administered during the diamide-evoked contraction completely inhibited the contraction to diamide. In conclusion, our results suggest that L-cysteine has markedly different effects in isolated whole-bladder preparations from neonatal and adult rats. Thus thiol-sensitive mechanisms may modulate contractility by regulation of Ca2+ and K+ channels and/or purinergic transmission in the neonatal bladder. The effects of L-cysteine and diamide were reversed in adult bladders, indicating that the regulation of bladder contractility by thiols is markedly altered during postnatal development.
本研究旨在比较巯基试剂 L-半胱氨酸和（二氮烯二羧酸双 5N，N-二甲基酰胺）二酰胺对新生和成年大鼠膀胱收缩活动的影响。使用来自 Wistar 大鼠的体外全膀胱制剂研究巯基试剂对自发性膀胱收缩的调节。在用阿托品和胍乙啶阻断胆碱能和肾上腺素能传递后，L-半胱氨酸促进新生大鼠膀胱的自发性膀胱收缩。二酰胺抑制 L-半胱氨酸的作用。二酰胺单独不改变新生大鼠膀胱的基础活性。L-半胱氨酸的促效作用被 L 型钙通道阻断剂硝苯地平和钙激活的钾通道 opener NS1619[1,3-二氢-1-[2-羟基-5-（三氟甲基）苯基]-5-（三氟甲基）-2H-苯并咪唑-2-酮]减少。ATP 或苏拉明，嘌呤能受体拮抗剂，显著抑制 L-半胱氨酸在新生膀胱中的作用，而一氧化氮合酶抑制剂 N（ω）-硝基-L-精氨酸无效。L-半胱氨酸在成年大鼠膀胱中未引起任何可检测的作用；而二酰胺引起大振幅持续紧张性收缩。当用 L-半胱氨酸预处理时，在成年膀胱中未发生二酰胺引起的收缩。此外，在二酰胺诱发的收缩期间给予 L-半胱氨酸完全抑制对二酰胺的收缩。总之，我们的结果表明，L-半胱氨酸在新生和成年大鼠的分离全膀胱制剂中具有明显不同的作用。因此，巯基敏感机制可能通过调节 Ca2+和 K+通道和/或嘌呤能传递来调节新生膀胱的收缩性。L-半胱氨酸和二酰胺的作用在成年膀胱中逆转，表明巯基对膀胱收缩性的调节在出生后发育过程中发生了明显改变。
