TY - JOUR T1 - Differential Effect of <span class="sc">l</span>-Cysteine in Isolated Whole-Bladder Preparations from Neonatal and Adult Rats JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 228 LP - 235 DO - 10.1124/jpet.109.161661 VL - 333 IS - 1 AU - Hacer S. G. Büyüknacar AU - Cemil Göçmen AU - William C. de Groat AU - Eda K. Kumcu AU - Hsi-Yang Wu AU - Serpil Önder Y1 - 2010/04/01 UR - http://jpet.aspetjournals.org/content/333/1/228.abstract N2 - 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 Nω-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. ER -