al-Hassani M H, Garcia J G, Gunst S J
Department of Physiology, Indiana University School of Medicine, Indianapolis 46202.
Am J Physiol. 1993 Jan;264(1 Pt 1):L53-9. doi: 10.1152/ajplung.1993.264.1.L53.
The muscarinic agonists acetylcholine (ACh) and McN-A-343 activate a homogeneous population of M3 receptors in canine tracheal smooth muscle. However, ACh is much more efficacious than McN-A-343 both at stimulating force development and active shortening and at antagonizing relaxation induced by isoproterenol. In other tissues, the same muscarinic receptor may be coupled to multiple subcellular pathways, but activate different pathways depending on the efficacy of the agonist. The present study investigated mechanisms of excitation-contraction coupling in canine tracheal smooth muscle by muscarinic agonists of different efficacy. ACh was more effective at stimulating inositol phosphate production and elicited a large initial transient increase in intracellular Ca2+ concentration ([Ca2+]i), whereas McN-A-343 elicited only a slow gradual rise in [Ca2+]i. Extracellular Ca2+ influx through voltage-operated channels played a minor role in contractions induced by either agonist. Results suggest that contractions by ACh and McN-A-343 may be mediated by the same subcellular pathways; however, the greater potency of ACh at stimulating those pathways results in very different kinetics of Ca2+ activation.
毒蕈碱激动剂乙酰胆碱（ACh）和 McN-A-343 可激活犬气管平滑肌中同质的 M3 受体群体。然而，在刺激张力发展和主动缩短以及拮抗异丙肾上腺素诱导的舒张方面，ACh 比 McN-A-343 更有效。在其他组织中，相同的毒蕈碱受体可能与多种亚细胞途径偶联，但根据激动剂的效力激活不同的途径。本研究通过不同效力的毒蕈碱激动剂研究了犬气管平滑肌中兴奋 - 收缩偶联的机制。ACh 在刺激肌醇磷酸生成方面更有效，并引起细胞内 Ca2+ 浓度（[Ca2+]i）的大幅初始瞬时升高，而 McN-A-343 仅引起 [Ca2+]i 的缓慢逐渐升高。通过电压门控通道的细胞外 Ca2+ 内流在两种激动剂诱导的收缩中起次要作用。结果表明，ACh 和 McN-A-343 引起的收缩可能由相同的亚细胞途径介导；然而，ACh 在刺激这些途径方面的更强效力导致 Ca2+ 激活的动力学非常不同。
