Effect of selective monoamine oxidase inhibition by clorgyline and deprenyl on the norepinephrine receptor-coupled adenylate cyclase system in rat cortex.
The consequences of selective monoamine oxidase (MAO) inhibition on the norepinephrine(NE)-sensitive adenylate cyclase system were determined in slices of rat cerebral cortex. The chronic administration of clorgyline, which selectively inhibited the activity of MAO-A, caused a significant decrease in the responsiveness of the noradrenergic cyclic AMP-generating system. The noradrenergic subsensitivity was accompanied by a significant decrease in the density of beta-adrenoceptors, as measured by 3H-dihydroalprenolol (DHA) binding, without altering the Kd value. However, selective inhibition of MAO-B by deprenyl did not alter the sensitivity of the cyclic AMP-generating system to NE or the specific DHA binding. The basal levels of cyclic AMP in the cortex were unaltered by the drugs. Since inhibition of MAO-A, but not MAO-B, increases the availability of NE, the results support the hypothesis that a persistent NE-receptor interaction is one of the prerequisites for the in vivo densitization of the NE-sensitive adenylate cyclase and the concomitant down-regulation of the number of beta-adrenoceptors in brain.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology; D003010:Clorgyline / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004082:Dihydroalprenolol; D007700:Kinetics; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects*; D012642:Selegiline / Q000494:pharmacology
D008996:Monoamine Oxidase Inhibitors; D011941:Receptors, Adrenergic; D012642:Selegiline; D004082:Dihydroalprenolol; D000242:Cyclic AMP; D008995:Monoamine Oxidase; D000262:Adenylyl Cyclases; D003010:Clorgyline