Induction of functional down-regulation of beta-adrenoceptors in rats by 2-phenylethylamine.
The effects of chronic administration of antidepressant drugs and 2-phenylethylamine on beta-adrenoceptor function were assessed. Monoamine oxidase inhibitors [phenelzine sulfate, 5 or 10 mg kg-1 per day, and (-)-deprenyl HCl, 1 mg kg-1 per day] and 2-phenylethylamine HCl (10 mg kg-1 per day) were administered to male Sprague-Dawley rats via Alzet osmotic minipumps. On days 21 and 22, the motor-suppressant actions of the beta-adrenoceptor agonist salbutamol hemisulfate (3 mg kg-1 intraperitoneally after 15 min) were assessed as a measure of beta-adrenoceptor sensitivity. On day 28, the animals were killed, and their brains were used for the measurement of monoamine oxidase activity and concentrations of 2-phenylethylamine, an endogenous amine and a metabolite of phenelzine. Phenelzine sulfate at 10 mg kg-1 per day (but not 5 mg kg-1 per day) and the combination of (-)-deprenyl and 2-phenylethylamine resulted in a decrease in the response to salbutamol. These treatments also resulted in substantial increases in brain 2-phenylethylamine concentrations. The phenelzine treatments each resulted in an equivalent inhibition of brain monoamine oxidase activity. These results support the proposal that 2-phenylethylamine may, at least in part, mediate the effects of phenelzine on beta-adrenoceptor function.
Department of Psychiatry, University of Alberta, Edmonton, Canada.
P R
PR
Paetsch
G B
GB
Baker
A J
AJ
Greenshaw
D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000201:enzymology / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D010624:Phenelzine / Q000494:pharmacology; D010627:Phenethylamines / Q000494:pharmacology*; D011619:Psychotropic Drugs / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D012642:Selegiline / Q000494:pharmacology
D010627:Phenethylamines; D011619:Psychotropic Drugs; D011943:Receptors, Adrenergic, beta; D012642:Selegiline; C029261:phenethylamine; D008995:Monoamine Oxidase; D010624:Phenelzine; D000420:Albuterol