Synergistic interaction between alpha- and beta-adrenergic receptors in rat brain slices: possible site for antidepressant drug action.
Experiments were undertaken to examine the characteristics of the adrenergic receptor-coupled cAMP system in rat brain slices. It was found that the potentiation of isoproterenol-stimulated cAMP accumulation by 6-fluoronorepinephrine, an alpha-adrenergic agonist, is largely dependent upon the degree of beta-receptor occupancy, with prazosin-sensitive alpha-adrenergic receptors contributing less to this interaction. Chronic administration of a variety of antidepressants decreased the potentiating interaction between 6-fluoronorepinephrine and isoproterenol even under conditions where there were no obvious effects on the alpha- or beta- adrenergic components themselves. Chronic administration of imipramine had no effect on the interaction between 6-fluoronorepinephrine and adenosine, suggesting that the drug selectively modifies the coupling between the alpha- and beta-adrenergic systems. The results suggest that antidepressants influence the coupling between 6-fluoronorepinephrine and isoproterenol receptors independent of any effect on the individual recognition sites.
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D004357:Drug Synergism; D007099:Imipramine / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009638:Norepinephrine / Q000031:analogs & derivatives / Q000494:pharmacology; D010293:Pargyline / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D000928:Antidepressive Agents; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; C024884:6-fluoronorepinephrine; D010293:Pargyline; D000242:Cyclic AMP; D007545:Isoproterenol; D007099:Imipramine; D009638:Norepinephrine