Roux F, Mavoungou E, Naline E, Lacroix H, Tordet C, Advenier C, Grandordy B M
Département de Pneumologie et de Physiologie Respiratoire, Hôpital Universitaire Cochin, Paris, France.
Am J Respir Crit Care Med. 1995 Jun;151(6):1745-51. doi: 10.1164/ajrccm.151.6.7767516.
Activation of muscarinic receptors in airway smooth muscle leads to breakdown of membrane polyphosphoinositides. In agreement with others, we show here that muscarinic stimulation elicits inositol-1,4,5-triphosphate formation. In addition, we show that carbachol also elicits total diacylglycerol and 1,2-sn diacylglycerol accumulation in a specific and dose-dependent manner (EC50 values: 2.1 x 10(-8) M for 1,2-sn diacylglycerol). The time-course of inositol-1,4,5-triphosphate accumulation is compatible with that of the clonic phase of muscle contraction. Since this derivative can mobilize intracellular Ca2+ stores, it may play a second-messenger role in the initial phase of contraction. The time-course of diacylglycerol accumulation is compatible with the muscarinic-induced tonic phase of smooth-muscle contraction. Carbachol induces similar dose-dependent reductions in isoproterenol-induced muscle relaxation (EC50 values for relaxation concentration-response curves to isoproterenol: 3 x 10(-6) M and 2.1 x 10(-5) M, with carbachol at 10(-7) M and 10(-4) M, respectively), and increases in adenylate cyclase activity (EC50 values for the concentration-response to isoproterenol: 1.2 x 10(-6) M and 1.5 x 10(-5) M, with carbachol at 10(-7) M and 10(-4) M, respectively). Since it is known that carbachol-induced uncoupling of beta 2-adrenergic receptors is proportional to the breakdown of polyphosphoinositides, and that 1,2-sn diacylglycerol is a potent activator of protein kinase C, 1,2-sn diacylglycerol could be mediating the uncoupling of beta 2-adrenergic receptors, via activation of alpha-protein kinase C and subsequent phosphorylation of receptor, and/or cyclase, and/or G proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
气道平滑肌中毒蕈碱受体的激活会导致膜多磷酸肌醇的分解。与其他人的研究结果一致，我们在此表明毒蕈碱刺激会引发肌醇 - 1,4,5 - 三磷酸的形成。此外，我们还表明卡巴胆碱也会以特定且剂量依赖的方式引发总二酰基甘油和1,2 - 二酰基 - sn - 甘油的积累（1,2 - 二酰基 - sn - 甘油的EC50值：2.1×10^(-8) M）。肌醇 - 1,4,5 - 三磷酸积累的时间进程与肌肉收缩的阵挛期一致。由于这种衍生物可以动员细胞内的钙储存，它可能在收缩的初始阶段起第二信使的作用。二酰基甘油积累的时间进程与毒蕈碱诱导的平滑肌收缩的强直期一致。卡巴胆碱在异丙肾上腺素诱导的肌肉舒张中引起类似的剂量依赖性降低（异丙肾上腺素舒张浓度 - 反应曲线的EC50值：分别为3×10^(-6) M和2.1×10^(-5) M，卡巴胆碱分别为10^(-7) M和10^(-4) M），并增加腺苷酸环化酶活性（异丙肾上腺素浓度 - 反应的EC50值：分别为1.2×10^(-6) M和1.5×10^(-5) M，卡巴胆碱分别为10^(-7) M和10^(-4) M）。已知卡巴胆碱诱导的β2 - 肾上腺素能受体解偶联与多磷酸肌醇的分解成比例，并且1,2 - 二酰基 - sn - 甘油是蛋白激酶C的有效激活剂，1,2 - 二酰基 - sn - 甘油可能通过激活α - 蛋白激酶C以及随后受体、环化酶和/或G蛋白的磷酸化来介导β2 - 肾上腺素能受体的解偶联。（摘要截短于250字）
