Enhancement of central and peripheral alpha 1-adrenoceptor sensitivity and reduction of alpha 2-adrenoceptor sensitivity following chronic imipramine treatment in rats.
After chronic imipramine treatment (20 mg/kg i.p., once daily for 14 days) the dose-response curve of the isolated rat anococcygeal muscle to phenylephrine shifted to the left, and furthermore, the -log KA value (affinity) for phenylephrine was significantly increased without affecting the affinity for guanfacine. On the other hand, such treatment caused a shift to the right of the dose-response curve to guanfacine on aortic strips and the affinity of the alpha-adrenoceptor for guanfacine was lowered without any accompanying changes in the affinity value for phenylephrine. However the relative efficacies of phenylephrine or guanfacine were not influenced by imipramine in either preparation. The ability of phenylephrine to displace [3H]prazosin from its specific binding sites was significantly enhanced after chronic imipramine treatment. These results may indicate that following chronic imipramine treatment the alpha 1-adrenoceptors of both central and peripheral tissues responded with supersensitivity to an alpha 1-preferential agonist, and the alpha 2-adrenoceptors with reduced sensitivity to an alpha 2-preferential agonist.
Hong
K W
KW
Rhim
B Y
BY
Lee
W S
WS
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D005260:Female; D007099:Imipramine / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009132:Muscles / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D007099:Imipramine; D011224:Prazosin