Calmodulin regulation of cholinergic muscarinic receptor: effects of calcium and phosphorylating states.
Calmodulin (CaM) regulation of cholinergic muscarinic receptor was investigated using synaptic membrane isolated from rat brains and [3H]-QNB as a binding ligand. CaM exerts a biphasic effect on receptor binding showing both a Ca2+-dependent receptor loss and an increase depending on the state of membrane phosphorylation. Calcineurin, a CaM-dependent protein phosphatase, mimicked the stimulatory effect of CaM in a dose-dependent manner. CaM-antagonists, W-7 and TFP reversed the stimulatory effect by CaM. A mechanism of protein phosphorylation and dephosphorylation of the cholinergic muscarinic receptors regulated by CaM-Ca2+ was proposed.
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002147:Calmodulin / Q000494:pharmacology*; D002148:Calmodulin-Binding Proteins / Q000494:pharmacology; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors; D010766:Phosphorylation; D011869:Radioligand Assay; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D013570:Synaptic Membranes / Q000378:metabolism
D002147:Calmodulin; D002148:Calmodulin-Binding Proteins; D011976:Receptors, Muscarinic; D010744:Phosphoric Monoester Hydrolases; D002118:Calcium