3-Methoxytyramine, an extraneuronal dopamine metabolite plays a physiological role in the brain as an inhibitory regulator of catecholaminergic activity.
3-Methoxytyramine (3-MT), an extraneuronal metabolite of dopamine, present in the synaptic cleft at a very low amount (low nanomolar range), comparable to dopamine concentration, is generally regarded as a biologically inactive compound. We have shown in this study that 3-MT binds to the rat noradrenergic cortical alpha(1) and striatal dopamine D(1) and D(2) receptors in nanomolar concentration range, and to cortical alpha(2) adrenoceptor at low micromolar concentration. Bilateral intrastriatal injections of 3-MT (0.25 micromol in 0.5 microl) did not affect significantly locomotor activity in naive rats but strongly antagonized amphetamine-induced (1 mg/kg s.c.) hypermotility. Biochemical studies in rat brain structures showed that 3-MT behaved as an antagonist of the noradrenergic system, i.e. accelerated noradrenaline metabolism and counteracted the inhibitory effect of amphetamine on the rate of noradrenaline metabolism. In contrast to a general view about the lack of physiological role of monoamine metabolites, these results for the first time strongly suggest that an extraneuronal metabolite of dopamine, 3-MT plays an important physiological role as an inhibitory regulator counteracting excessive stimulation of catecholaminergic neurons in the striatum.
Antkiewicz-Michaluk
Lucyna
L
Department of Neurochemistry, Institute of Pharmacology Polish Academy of Sciences, Smetna 12, 31-052 Kraków, Poland. antkiew@if-pan.krakow.pl
Ossowska
Krystyna
K
Romańska
Irena
I
Michaluk
Jerzy
J
Vetulani
Jerzy
J
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects* / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects* / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism
D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D000661:Amphetamine; C001746:3-methoxytyramine; D004298:Dopamine; D009638:Norepinephrine