Chronic exposure of C6 glioma cells to desipramine desensitizes beta-adrenoceptors, but increases KL/KH ratio.
Incubation of rat glioma C6 cells with 10 microM desipramine for five days in vitro resulted in a 31% reduction of beta-adrenoceptors and a 38% reduction in isoproterenol-stimulated cyclic AMP accumulation. In contrast, forskolin or cholera toxin-stimulated cyclic AMP was unaffected by desipramine. Surprisingly, the beta-adrenoceptor desensitization was accompanied by an increase in the ratio of dissociation constants (KL/KH) for the low and high affinity states of the beta-adrenoceptor respectively and supports the concept of a complex interaction between the receptor and Gs protein.
Manji
H K
HK
Section on Clinical Pharmacology, National Institute of Mental Health, Bethesda, MD 20892.
Chen
G A
GA
Bitran
J A
JA
Gusovsky
F
F
Potter
W Z
WZ
D000818:Animals; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D003891:Desipramine / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D002772:Cholera Toxin; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D007545:Isoproterenol; D003891:Desipramine