The effects of chronic administration of inhibitors of flavin and quinone amine oxidases on imidazoline I(1) receptor density in rat whole brain.
Many imidazoline ligands have been shown to bind to the active sites of several amine oxidases, and endogenous ligands such as agmatine and tryptamine are amine oxidase substrates. In order to ascertain whether concentrations of endogenous imidazoline receptor agonists might be regulated by amine oxidase activities, rats were administered saline, clorgyline, deprenyl, MDL 72274A, aminoguanidine, or a combination of clorgyline, deprenyl, and aminoguanidine, for 14 days, and then binding parameters for [(3)H]clonidine at imidazoline I(1) receptors were determined in whole brain. Several EC 1.4.3.4, 1.4.3.6, and 1.5.3.11 amine oxidase activities were also measured ex vivo in tissues from treated animals. Results showed that drug treatments did not alter the affinity of clonidine for imidazoline I(1) receptors. There was a tendency toward a reduction in receptor density when monoamine oxidase (MAO)-A 1 MAO-B, MAO-B 1 semicarbazide-sensitive amine oxidase (SSAO), or SSAO 1 diamine oxidase (DAO) were inhibited, and a marked reduction in density when MAO-A 1 MAO-B 1 SSAO were inhibited. These data suggest that amines that are substrates both for MAO and for SSAO, such as tryptamine and other trace amines, may act as endogenous imidazoline I(1) receptor agonists, at which they may have neuromodulatory efficacy. A role for beta-carbolines, which can form endogenously from tryptamine, is also supported by the present findings.
Holt
Andrew
A
Neurochemical Research Unit, Department of Psychiatry, 1E7.44 Walter C. Mackenzie Health Sciences Centre, University of Alberta, Edmonton, Alberta, Canada T6G 2B7. aholt@alviva.ca
Todd
Kathryn G
KG
Baker
Glen B
GB
D000316:Adrenergic alpha-Agonists / Q000378:metabolism; D000498:Allyl Compounds / Q000494:pharmacology; D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003000:Clonidine / Q000378:metabolism; D003010:Clorgyline / Q000494:pharmacology; D004338:Drug Combinations; D006146:Guanidines / Q000494:pharmacology; D054755:Imidazoline Receptors; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000378:metabolism* / Q000494:pharmacology; D011437:Propylamines / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000378:metabolism*; D012642:Selegiline / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000498:Allyl Compounds; D004338:Drug Combinations; D006146:Guanidines; D054755:Imidazoline Receptors; C090015:MDL 72274A; D008996:Monoamine Oxidase Inhibitors; D011437:Propylamines; D011955:Receptors, Drug; C410887:imidazoline I1 receptors; D012642:Selegiline; D006631:Amine Oxidase (Copper-Containing); D008995:Monoamine Oxidase; D003010:Clorgyline; D003000:Clonidine; C004479:pimagedine