Isoprenaline-induced changes in type I inhibitor activity as an index of beta-adrenergic receptor subsensitivity.
Isoprenaline produced a dose-dependent decrease in the activity of an endogenous, specific inhibitor of cAMP-dependent protein kinase (type I inhibitor) in rat hippocampus, brain stem and pineal gland. Prolonged, 21-days treatment with some antidepressant (imipramine, nomifensin and mianserin) markedly reduced the response of the type I inhibitor activity to isoprenaline. To obtain the significant decrease of the type I inhibitor activity, five times higher dose of isoprenaline had to be used in these animals than in control rats. Mianserin is known to produce a decrease of the activity of adenylate cyclase coupled to beta-adrenergic receptors without changing the number of receptor binding sites. In the present study we have shown that also mianserin after prolonged treatment produces subsensitivity of beta-adrenergic receptors when measured by the response of the type I inhibitor activity to isoprenaline. Single doses of imipramine, nomifensin and mianserin did not change the isoprenaline-induced decrease of the type I inhibitor activity. It seems that the isoprenaline-induced decreased of the type I inhibitor activity can be used as an index of beta-adrenergic receptor reactivity.
D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D001933:Brain Stem / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D007099:Imipramine / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D008803:Mianserin / Q000494:pharmacology; D009627:Nomifensine / Q000494:pharmacology; D010870:Pineal Gland / Q000378:metabolism; D047428:Protein Kinase Inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D047428:Protein Kinase Inhibitors; D011943:Receptors, Adrenergic, beta; C015482:protein kinase modulator; D009627:Nomifensine; D008803:Mianserin; D000628:Aminophylline; D007545:Isoproterenol; D007099:Imipramine