PT  - JOURNAL ARTICLE
AU  - R A Keith
AU  - B B Howe
AU  - A I Salama
TI  - 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.
DP  - 1986 Feb 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 356--363
VI  - 236
IP  - 2
4099  - http://jpet.aspetjournals.org/content/236/2/356.short
4100  - http://jpet.aspetjournals.org/content/236/2/356.full
SO  - J Pharmacol Exp Ther1986 Feb 01; 236
AB  - 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)