Carbachol induces desensitization of cardiac beta-adrenergic receptors through muscarinic M1 receptors.
Incubation of enzymatically dissociated cardiac myocytes with carbachol leads to a time- and concentration-dependent loss of beta-receptors assayable with [3H]CGP-12177. This loss is due to a redistribution of beta-receptors from the plasma membrane to a cytosol-derived vesicular fraction, consistent with an internalization process. The carbachol effects are not influenced by gallamine or oxotremorine which interact with the high-affinity (M2) muscarinic receptors. These results suggest that carbachol-induced desensitization is secondary to activation of protein kinase C by diacylglycerols generated through M1 receptor-linked phosphoinositide hydrolysis.
Limas
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Limas
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D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D004075:Diglycerides / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005703:Gallamine Triethiodide / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D010095:Oxotremorine / Q000494:pharmacology; D011412:Propanolamines / Q000378:metabolism; D011493:Protein Kinase C; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution
D004075:Diglycerides; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic; D010095:Oxotremorine; D002217:Carbachol; D011494:Protein Kinases; D011493:Protein Kinase C; D005703:Gallamine Triethiodide; C033394:CGP 12177