Lanzafame A A, Christopoulos A, Mitchelson F
Department of Pharmacology, The University of Melbourne, Victoria, Australia.
Recept Channels. 2003;9(4):241-60.
Signaling pathways for muscarinic acetylcholine receptors (mAChRs) include several enzymes and ion channels. Recent studies have revealed the importance of various isoforms of both alpha and betagamma subunits of G proteins in initiation of signaling as well as the role of the small monomeric G protein, Rho, in the activation of phospholipase D. Modulation of adenylyl cyclase activity by mAChRs appears more diverse as the interaction of various receptor subtypes with the many isoforms of the enzyme are studied. Both alpha and beta subunits of G(i/o) may be involved. Some mAChR responses arise through release of nitric oxide from nitrergic nerves, including salivary gland secretion and hippocampal slow wave activity. mAChRs utilize a variety of intracellular pathways to activate various mitogen-activated protein kinases. The kinases are involved in cholinergic regulation of kidney epithelial function, catabolism of amyloid precursor protein, hippocampal long-term potentiation, activation of phospholipase A(2), and gene induction. mAChR activation can also stimulate or inhibit cellular growth and apoptosis, dependent on prior levels of cellular activity. Modulation of ion channels by mAChR agonists appears increasingly complex, based on recent studies. K(+) channels may be activated by M(2) and M(4) mAChR stimulation, although in the rat superior cervical ganglion topographical constraints appear to limit the effect to the M(2) mAChR. Another ganglionic K(+) current, the M current, is inhibited by M(1) mAChR activation, but in murine hippocampus inhibition involves another receptor subtype. R-type Ca(2+) channels are both facilitated and inhibited by M(1) and M(2) mAChRs; facilitation being more pronounced with activation of M(1) mAChRs and inhibition with M(2) mAChRs.
毒蕈碱型乙酰胆碱受体（mAChRs）的信号通路包括多种酶和离子通道。最近的研究揭示了G蛋白的α和βγ亚基的各种同工型在信号起始中的重要性，以及小的单体G蛋白Rho在磷脂酶D激活中的作用。随着对各种受体亚型与该酶的多种同工型相互作用的研究，mAChRs对腺苷酸环化酶活性的调节似乎更加多样。G(i/o)的α和β亚基可能都参与其中。一些mAChR反应是通过从含氮神经释放一氧化氮产生的，包括唾液腺分泌和海马慢波活动。mAChRs利用多种细胞内途径来激活各种丝裂原活化蛋白激酶。这些激酶参与肾上皮功能的胆碱能调节、淀粉样前体蛋白的分解代谢、海马长时程增强、磷脂酶A(2)的激活以及基因诱导。mAChR激活还可以刺激或抑制细胞生长和凋亡，这取决于细胞活动的先前水平。基于最近的研究，mAChR激动剂对离子通道的调节似乎越来越复杂。K(+)通道可能通过M(2)和M(4) mAChR刺激而被激活，尽管在大鼠颈上神经节中，地形限制似乎将这种作用限制在M(2) mAChR。另一种神经节K(+)电流，即M电流，被M(1) mAChR激活所抑制，但在小鼠海马中，抑制涉及另一种受体亚型。R型Ca(2+)通道受到M(1)和M(2) mAChRs的促进和抑制；M(1) mAChR激活时促进作用更明显，M(2) mAChR激活时抑制作用更明显。
