Quinn Teresa, Collins Colm, Baird Alan W
Department of Veterinary Physiology and Biochemistry, Faculty of Veterinary Medicine, University College Dublin, Ireland.
BJU Int. 2004 Sep;94(4):651-7. doi: 10.1111/j.1464-410X.2004.05017.x.
To investigate the mechanisms of neurokinin A- and substance P-induced contractions of rat urinary bladder smooth muscle, and to compare them with those of the muscarinic agonist carbachol.
Rat urinary bladder strips were suspended under 1 g of tension in a physiological buffer at 37 degrees C, gassed with 95% O(2)/5% CO(2). Mechanical activity was recorded isometrically during exposure to neurokinin A and substance P.
Both agents produced concentration-dependent contractions of smooth muscle strips which were unaffected by tetrodotoxin (1 micro mol/L), peptidase inhibitors (captopril, thiorphan and bestatin; 1 micro mol/L each) or piroxicam (10 micro mol/L). The rank order of potency of agonists was neurokinin A > substance P > carbachol. Contractile responses to neurokinin A and substance P, like the contractile responses to carbachol, were abolished in a nominally Ca(2+)-free medium and significantly reduced by nifedipine (1 micro mol/L). SKF-96365 (60 micro mol/L), an inhibitor of receptor-mediated Ca(2+) entry, abolished the nifedipine-resistant response to substance P and carbachol, and significantly attenuated the response to neurokinin A. Depleting intracellular Ca(2+) stores with thapsigargin (1 micro mol/L) significantly attenuated neurokinin A-induced contractions but had no effect on substance P- or carbachol- induced contractions. The Rho-kinase inhibitor, Y-27632 (10 micro mol/L), significantly reduced both phasic and tonic components of the contractile responses to neurokinin A, substance P and carbachol.
The contractile responses induced by tachykinins in rat urinary bladder smooth muscle strips involve a direct action on smooth muscle and are not modulated by peptidases or prostanoids. Neurokinin A and substance P, like carbachol-induced contractions, depend on extracellular Ca(2+) influx largely through voltage-operated and partly through receptor-operated Ca(2+) channels. Intracellular Ca(2+) release contributes to the contractile response to neurokinin A but appears to have no involvement in substance P- and carbachol-induced contractions. Rho-kinase activation contributes to contractions induced by substance P, neurokinin A and carbachol.
研究神经激肽A和P物质诱导大鼠膀胱平滑肌收缩的机制，并将其与毒蕈碱激动剂卡巴胆碱的作用机制进行比较。
将大鼠膀胱条带在37℃的生理缓冲液中以1g的张力悬挂，用95%O₂/5%CO₂通气。在暴露于神经激肽A和P物质期间等长记录机械活动。
两种药物均引起平滑肌条带浓度依赖性收缩，不受河豚毒素（1μmol/L）、肽酶抑制剂（卡托普利、噻吗洛尔和贝司他汀；各1μmol/L）或吡罗昔康（10μmol/L）的影响。激动剂的效力顺序为神经激肽A＞P物质＞卡巴胆碱。在名义上无钙的培养基中，对神经激肽A和P物质的收缩反应，如同对卡巴胆碱的收缩反应一样，均被消除，且硝苯地平（1μmol/L）使其显著减弱。受体介导的钙内流抑制剂SKF-96365（60μmol/L）消除了对P物质和卡巴胆碱的硝苯地平抵抗反应，并显著减弱了对神经激肽A的反应。用毒胡萝卜素（1μmol/L）耗尽细胞内钙储存显著减弱神经激肽A诱导的收缩，但对P物质或卡巴胆碱诱导的收缩无影响。Rho激酶抑制剂Y-27632（10μmol/L）显著降低了对神经激肽A、P物质和卡巴胆碱收缩反应的相性和紧张性成分。
速激肽在大鼠膀胱平滑肌条带中诱导的收缩反应涉及对平滑肌的直接作用，且不受肽酶或前列腺素的调节。神经激肽A和P物质，如同卡巴胆碱诱导的收缩一样，很大程度上依赖细胞外钙内流，主要通过电压门控钙通道，部分通过受体门控钙通道。细胞内钙释放参与对神经激肽A诱导的收缩反应，但似乎不参与P物质和卡巴胆碱诱导的收缩。Rho激酶激活参与P物质、神经激肽A和卡巴胆碱诱导的收缩。
