Differential Effect of l-Cysteine in Isolated Whole-Bladder Preparations from Neonatal and Adult Rats

Abstract

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 Ca 2ϩ channel-blocking agent nifedipine and the calciumactivated K ϩ 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 -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 wholebladder preparations from neonatal and adult rats. Thus thiol-sensitive mechanisms may modulate contractility by regulation of Ca 2ϩ and K ϩ 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.

Vasoactivity of the gasotransmitters hydrogen sulfide and carbon monoxide in the chicken ductus arteriosus

“…Taken together, these findings suggest that L-cysteine elicits contraction of PulmDA rings by promoting Ca 2ϩ influx via nifedipinesensitive Ca 2ϩ channels and intracellular Ca 2ϩ release from the sarcoendoplasmic reticulum. Our results are consistent with the data obtained in both smooth and striated muscle, which indicate that L-cysteine is an important modulator of Ca 2ϩ homeostasis (13,21,54). We also observed that neither the CSE inhibitor PPG nor the CBS inhibitor AOA significantly affected L-cysteine-induced contraction of PulmDA rings.…”

The validation of a functional, isolated pig bladder model for physiological experimentation

“…Thus, to interpret findings from small isolated preparations requires them to be validated with whole organ preparations. To date most of this work has used bladders from small rodents maintained in physiological saline environments (Drake et al, 2003a ; Gillespie et al, 2003 ; Fabiyi and Brading, 2006 ; Buyuknacar et al, 2010 ). Extrapolating findings generated using small laboratory animals to the physiology of urine storage and voiding in large animals and the clinical context is difficult, and requires validation as additional issues have to be reconciled such as: differences in the base-line physiological properties of larger bladders and experimental considerations (adequate tissue perfusion and environmental control).…”

Developmental and spinal cord injury‐induced changes in nitric oxide‐mediated inhibition in rat urinary bladder

“…The pharmacology of the rat urinary bladder also changes during postnatal development. For example, the neonatal rat bladder (10–21 days) is very sensitive to the inhibitory effect of nitric oxide5 and the excitatory effect of L ‐cysteine 6. These effects appear to be markedly diminished during postnatal development as they have not been detected in bladders from adult rats 6–8.…”