Rasmussen H, Kelley G, Douglas J S
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven 06510.
Am J Physiol. 1990 Jun;258(6 Pt 1):L279-88. doi: 10.1152/ajplung.1990.258.6.L279.
Cholinergic stimuli acting via muscarinic receptors stimulate airway smooth muscle to contract and beta-adrenergic stimuli induce it to relax. Cholinergic agonists stimulate intracellular Ca2+ release and Ca2+ influx, and beta-adrenergic agonists stimulate adenosine 3',5'-cyclic monophosphate (cAMP) production. Since it was found that cAMP alters cholinergic agonist-induced changes in cellular Ca2+ metabolism, it was postulated that cAMP brought about a relaxation of this smooth muscle primarily by altering Ca2+ metabolism. More recently, it has become clear that when cholinergic agonists, as well as histamine and serotonin, act, the hydrolysis of polyphosphoinositols is stimulated, diacylglycerol production is increased, and coordinated changes in Ca2+ metabolism and protein kinase function occur. These agonists also act to inhibit adenylate cyclase activity. Conversely, it has been found that in the absence of agonist activation, cAMP increases Ca2+ influx without stimulating contraction and that in the presence of muscarinic agonists, it acts to inhibit polyphosphoinositide hydrolysis. In addition, cAMP has been shown to alter the state of phosphorylation of a number of cellular proteins, an effect that is independent of any effect on cellular Ca2+ metabolism. Based on these newer data, an expanded model of Ca2(+)-cAMP interactions in the regulation of airway smooth muscle tone is presented. A key feature of this model is the operation of dual, reciprocal inhibitory signals by which the Ca2+ and cAMP messenger systems modulate each other's expression.
通过毒蕈碱受体起作用的胆碱能刺激会刺激气道平滑肌收缩，而β-肾上腺素能刺激则诱导其舒张。胆碱能激动剂刺激细胞内钙离子释放和钙离子内流，而β-肾上腺素能激动剂刺激腺苷3',5'-环磷酸（cAMP）生成。由于发现cAMP会改变胆碱能激动剂诱导的细胞钙离子代谢变化，因此推测cAMP主要通过改变钙离子代谢使这种平滑肌舒张。最近，已经明确当胆碱能激动剂以及组胺和5-羟色胺起作用时，多磷酸肌醇的水解受到刺激，二酰基甘油生成增加，并且钙离子代谢和蛋白激酶功能发生协同变化。这些激动剂还会抑制腺苷酸环化酶活性。相反，已经发现，在没有激动剂激活的情况下，cAMP会增加钙离子内流而不刺激收缩，并且在存在毒蕈碱激动剂的情况下，它会抑制多磷酸肌醇水解。此外，cAMP已被证明会改变许多细胞蛋白的磷酸化状态，这种作用独立于对细胞钙离子代谢的任何影响。基于这些新数据，提出了一个在气道平滑肌张力调节中Ca2(+)-cAMP相互作用的扩展模型。该模型的一个关键特征是双重、相互抑制信号的运作，通过该信号钙离子和cAMP信使系统相互调节对方的表达。
