Downregulation of M1 and M2 Muscarinic Receptor Subtypes in Y1 Mouse Adrenocarcinoma Cells

摘要: Muscarinic acetylcholine receptors are important in mediating neurotransmission the central and peripheral nervous systems regulate a broad spectrum of physiologic responses. Chronic exposure cells to muscarinic agonists results decrease receptor number diminished coupling effectors. We examined this phenomenon 2 5 described subtypes: ml, one predominant subtypes expressed brain, m2, major cardiac subtype. DNA clones for these were transfected into Y1 mouse adrenal cell line variant clone. Kin 8, which cAMP-dependent protein kinase activity is greatly reduced. Transfected could be at high levels functional as determined by their ability bind ligands stimulate phosphoinositide turnover (ml) or inhibit adenylyl cyclase (m2). susceptibility internalization after chronic agonist, carbachol, consequence activation C. These experiments suggest that mechanisms m1 m2 differ. The but not was internalized response C dependent on presence kinase. Activation either did mimic agonist-induced m2. There large surplus effector enzymes expressing several hundred fmol per mg membrane protein. At low numbers, desensitization correlated with receptors.