Supersensitive beta-adrenergic receptors are down-regulated in rat brain by mianserin administration.
Experiments were undertaken to determine whether alterations in rat brain monoaminergic tone influence the manner in which mianserin administration modifies beta-adrenergic receptor function. Whereas the chronic administration of mianserin had little effect on isoproterenol-stimulated cAMP accumulation in control cerebral cortical slices, treatment with this antidepressant prevented or reversed beta-adrenergic receptor super-sensitivity resulting from reserpine or 6-hydroxydopamine administration. In contrast, 5,7 dihydroxytryptamine treatment had no effect on beta-adrenergic receptor activity, or on the ability of mianserin to modify isoproterenol-stimulated cAMP accumulation. The results indicate that antidepressant-induced alterations in beta-adrenergic receptor activity may, in some cases, be a function of receptor sensitivity at the time of drug administration.
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Department of Pharmacology, University of Texas Medical School, Houston.
Enna
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SJ
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D006892:Hydroxydopamines / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008803:Mianserin / Q000494:pharmacology*; D009638:Norepinephrine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D012701:Serotonin / Q000378:metabolism
D006892:Hydroxydopamines; D011943:Receptors, Adrenergic, beta; D008803:Mianserin; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; C024884:6-fluoronorepinephrine; D016627:Oxidopamine; D000242:Cyclic AMP; D007545:Isoproterenol; D009638:Norepinephrine