Membrane phospholipid polar heads influence the coupling of M2 muscarinic receptors to G proteins.
Treating membranes from rat heart with phospholipase C (phosphatidylcholine choline phosphohydrolase) from Clostridium perfringens increased the affinity of muscarinic acetylcholine receptors (M2) for the agonists carbachol and oxotremorine. The affinity for antagonists was not affected. Phospholipase C activity, i.e., the cleavage of polar heads of membrane phospholipids, led to the disappearance of the guanine nucleotide-dependent rightward shift of the isotherm for agonist binding. The treatment of tracheal smooth muscle with phospholipase C led to a decrease in the maximum contractile effect of muscarinic (M2) stimulation with no modification of the agonist EC50, i.e., to the uncoupling of the stimulation-contraction process. These results demonstrate that when phospholipid polar heads are hydrolysed by phospholipase C, M2 receptors are uncoupled from G proteins, which enhances their affinity for agonists but prevents information transfer.
D000818:Animals; D002217:Carbachol / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000494:pharmacology*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism*; D010095:Oxotremorine / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D010738:Type C Phospholipases / Q000494:pharmacology
D008565:Membrane Proteins; D010743:Phospholipids; D011976:Receptors, Muscarinic; D006165:Guanylyl Imidodiphosphate; D010095:Oxotremorine; D002217:Carbachol; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins