Desensitization of muscarinic receptors.
When Chinese hamster ovary cells transfected with the gene for M(3)-muscarinic receptors were stimulated with carbachol continuously for 30 min, the response at the end of the stimulation period was about 20% of the early response (2-3 min after the start of the stimulation). Long-term treatment of the cells with phorbol ester abolished the response completely while desensitization was significantly reduced upon pre-treatment of the cells with GF109203X, antisense oligonucleotide against the alpha-isoform of protein kinase C and wortmannin. We conclude that in the Chinese hamster ovary expression system, desensitization of M(3)-muscarinic receptors is dependent on a fast feedback loop including the alpha-isoform of protein kinase C.
Fraeyman
N
N
Heymans Institute for Pharmacology, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium. norbert.fraeyman@UGent.be
van Emmelo
J
J
Paulssen
R H
RH
Vermis
K
K
D000818:Animals; D016466:CHO Cells; D002217:Carbachol / Q000494:pharmacology*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D018721:Muscarinic Agonists / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011976:Receptors, Muscarinic / Q000378:metabolism*; D013395:Sucrose / Q000378:metabolism
D018721:Muscarinic Agonists; D011976:Receptors, Muscarinic; D013395:Sucrose; D002217:Carbachol; D011493:Protein Kinase C