Emala C W, Aryana A, Levine M A, Yasuda R P, Satkus S A, Wolfe B B, Hirshman C A
Department of Anesthesiology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA.
Am J Physiol. 1995 Jun;268(6 Pt 1):L935-40. doi: 10.1152/ajplung.1995.268.6.L935.
Airway smooth muscle from asthmatic humans and from the Basenji-greyhound dog (BG) dog is hyporesponsive to beta-adrenergic agonist stimulation. Because adenylyl cyclase is under dual regulation in airway smooth muscle, we compared muscarinic receptor-coupled inhibition of adenylyl cyclase in airway smooth muscle from BG and mongrel dogs. Inhibition of forskolin-stimulated adenylyl cyclase activity by the muscarinic M2 agonist oxotremorine was greater in airway smooth muscle membranes from BG compared with mongrel controls. Quantitative immunoprecipitation studies showed increased numbers of m2 but not m3 muscarinic receptors in the BG airway smooth muscle. The enhanced ability of muscarinic agonists to inhibit adenylyl cyclase in BG airway smooth muscle may be due to the greater numbers of muscarinic m2 receptors, which may account in part for impaired airway smooth muscle relaxation in the BG model of airway hyperresponsiveness.
来自哮喘患者以及巴仙吉 - 灵缇犬(BG犬)的气道平滑肌对β - 肾上腺素能激动剂刺激反应低下。由于腺苷酸环化酶在气道平滑肌中受到双重调节,我们比较了BG犬和杂种犬气道平滑肌中毒蕈碱受体偶联的腺苷酸环化酶抑制作用。与杂种犬对照组相比,毒蕈碱M2激动剂氧化震颤素对BG犬气道平滑肌膜中福斯可林刺激的腺苷酸环化酶活性的抑制作用更强。定量免疫沉淀研究表明,BG犬气道平滑肌中M2毒蕈碱受体数量增加,而M3毒蕈碱受体数量未增加。毒蕈碱激动剂在BG犬气道平滑肌中抑制腺苷酸环化酶的能力增强可能是由于毒蕈碱M2受体数量较多,这可能部分解释了BG犬气道高反应性模型中气道平滑肌舒张受损的原因。