Down-regulation of beta-adrenergic and dopaminergic receptors induced by 2-phenylethylamine.
1. The effects of chronic administration (28 days s.c. via Alzet osmotic minipumps) of 2-phenylethylamine.HCl (10 mg kg-1 per day) and/or (-)-deprenyl.HCl (1 mg kg-1 per day) on dopamine and noradrenaline receptor subtypes have been measured in rat brain. 3H-CGP 12177 was used to label beta-adrenoceptors; 3H-spiperone and 3H-SCH 23390 were used to label D2-like and D1-like receptors. 2. Total cortical beta-adrenoceptor density was reduced by (-)-deprenyl but not 2-phenylethylamine alone. Combined administration of 2-phenylethylamine and (-)-deprenyl resulted in a significantly larger decrease than (-)-deprenyl alone. Subtype density analysis by competition experiments with ICI 89406 revealed that the (-)-deprenyl effect in cortex was due to a decrease in beta 1-adrenoceptor density. The combination of 2-phenylethylamine and (-)-deprenyl resulted in a significant decrease in both cortical beta 1- and cortical beta 2-adrenoceptors. Cerebellar beta-adrenoceptor density was not altered by the present drug treatments. The Kd values for total beta-adrenoceptor densities and Ki values for beta-adrenoceptor subtype densities were not altered by drug treatment in either cortex or cerebellum. 3. Administration of 2-phenylethylamine and of (-)-deprenyl resulted in a decrease in the density of D1-like 3H-SCH 23390 but not D2-like 3H-spiperone binding to dopamine receptors in the striatum. The effects of combined 2-phenylethylamine and (-)-deprenyl treatment on 3H-SCH 23390 binding were additive. These drug treatments did not alter Kd values for these binding sites. 4. The down-regulation of catecholamine receptors following chronically increased availability of 2-phenylethylamine may be due to the catecholamine releasing or uptake blocking effects of this amine. These effects may also be attributable to a direct neuromodulatory action of 2-phenylethylamine on catecholamine receptors. 5. The parallels between effects of increased 2-phenylethylamine availability and effects of administration of MAO inhibitor antidepressants on catecholamine receptor systems indicate that this substrate for MAO may mediate some of the effects of MAO inhibitor antidepressants.
Paetsch
P R
PR
Department of Psychiatry, University of Alberta, Edmonton, Canada.
Greenshaw
A J
AJ
D000818:Animals; D001552:Benzazepines / Q000378:metabolism; D001667:Binding, Competitive; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004357:Drug Synergism; D008297:Male; D009928:Organ Specificity; D010627:Phenethylamines / Q000494:pharmacology*; D011412:Propanolamines / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000096:biosynthesis / Q000145:classification / Q000187:drug effects*; D011954:Receptors, Dopamine / Q000096:biosynthesis / Q000187:drug effects*; D012642:Selegiline / Q000494:pharmacology; D013134:Spiperone / Q000378:metabolism
D001552:Benzazepines; D010627:Phenethylamines; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D011954:Receptors, Dopamine; D012642:Selegiline; C029261:phenethylamine; D013134:Spiperone; C033394:CGP 12177