Modulation of peripheral beta-1 and alpha-2 receptor sensitivities by the administration of the tricyclic antidepressant, imipramine, alone and in combination with alpha-2 antagonists to rats.
The purpose of the present investigation was to determine whether peripheral beta-1 and alpha-2 receptors are regulated by the tricyclic antidepressant, imipramine. The administration of imipramine alone decreased the sensitivity of peripheral beta-1 receptor activity in anesthetized rats (isoproterenol-induced positive chronotropy) after 11 days, but not after 4 days. The coadministration of the selective alpha-2 antagonists, yohimbine or idazoxan (RX 781094), with imipramine resulted in a decrease in beta-1 receptor sensitivity in anesthetized rats within only 4 days. In isolated spontaneously beating right atria taken from drug-treated rats, beta-1 receptor sensitivity (isoproterenol positive chronotrophy) was not affected by the administration of imipramine for 4 days; however, administration of imipramine for 11 days resulted in significant decrease in beta-1 receptor sensitivity. The coadministration of yohimbine or idazoxan with imipramine resulted in a decrease in beta-1 receptor function in only 4 days. Beta-2 receptor sensitivity (isoproterenol-induced hypotension in anesthetized rats) was not significantly altered under conditions in which beta-1 receptor sensitivity was decreased. The destruction of central catecholamine-containing neurons with 6-hydroxydopamine prevented the subsensitivity of peripheral beta-1 receptor function in anesthetized rats induced by the coadministration of imipramine plus yohimbine (4 days). The sensitivity of peripheral alpha-2 receptors (clonidine-induced inhibition of electrically stimulated rat vas deferens) was depressed after the administration of imipramine alone (4 days) and imipramine plus yohimbine or idazoxan (4 days).(ABSTRACT TRUNCATED AT 250 WORDS)
Keith
R A
RA
Howe
B B
BB
Salama
A I
AI
D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects; D004146:Dioxanes / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006892:Hydroxydopamines / Q000494:pharmacology; D019329:Idazoxan; D007099:Imipramine / Q000008:administration & dosage / Q000494:pharmacology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D016627:Oxidopamine; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000032:analysis / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000032:analysis / Q000187:drug effects* / Q000502:physiology; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D006892:Hydroxydopamines; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D015016:Yohimbine; D016627:Oxidopamine; D007545:Isoproterenol; D007099:Imipramine; D019329:Idazoxan