Idazoxan down-regulates beta-adrenoceptors on C6 glioma cells in vitro.
Incubation of the C6 cells with 10 microM idazoxan (an alpha 2-adrenoceptor antagonist and putative antidepressant) for 5 days in vitro resulted in a 23% reduction of beta-adrenoceptor number and a 37% decrease in isoproterenol-induced cyclic AMP accumulation. In contrast, post-receptor stimulated cyclic AMP accumulation (by the use of forskolin or cholera toxin) was unaffected. The desensitization of the beta-adrenoceptor was accompanied by an increase in the KL/KH ratio for this receptor. Chronic in vitro treatment of C6 glioma cells with idazoxan did not significantly affect cholera or pertussis toxin catalyzed ribosylation of Gs and Gi/Go in these cells. Similarly, idazoxan did not alter either the basal levels of protein kinase C (PKC) alpha, or its cytoplasm to membrane translocation. These results suggest that idazoxan may have direct postsynaptic effects, the site of which may be at the level of receptor/G protein interaction.
Section on Clinical Pharmacology, National Institute of Mental Health, Bethesda, MD 20892.
H K
HK
Manji
G
G
Chen
J A
JA
Bitran
F
F
Gusovsky
W Z
WZ
Potter
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001345:Autoradiography; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004146:Dioxanes / Q000494:pharmacology*; D015536:Down-Regulation; D005910:Glioma / Q000378:metabolism; D019329:Idazoxan; D007545:Isoproterenol / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000378:metabolism
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D002772:Cholera Toxin; D000242:Cyclic AMP; D011493:Protein Kinase C; D007545:Isoproterenol; D019329:Idazoxan