Primate trace amine receptor 1 modulation by the dopamine transporter.
Article Details
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Miller GM, Verrico CD, Jassen A, Konar M, Yang H, Panas H, Bahn M, Johnson R, Madras BK
Primate trace amine receptor 1 modulation by the dopamine transporter.
J Pharmacol Exp Ther. 2005 Jun;313(3):983-94. Epub 2005 Mar 11.
- PubMed ID
- 15764732 [ View in PubMed]
- Abstract
Recently identified trace amine receptors are potential direct targets for drugs of abuse, including amphetamine and 3,4-methylenedioxymethamphetamine (MDMA). We cloned full-length rhesus monkey trace amine receptor 1 (rhTA(1)) that was 96% homologous to human TA(1). The trace amines tyramine and beta-phenylethylamine (PEA) and the monoamine transporter substrates (+/-)-amphetamine and (+/-)-MDMA stimulated cAMP accumulation in rhTA(1)-expressing cell lines, as measured by a cAMP response element-luciferase assay. Cocaine did not stimulate cAMP accumulation in rhTA(1) cells, but it blocked [(3)H]PEA transport mediated by the dopamine transporter. Cotransfection with the human dopamine transporter enhanced PEA-, amphetamine-, and MDMA-mediated rhTA(1) receptor activation, but it diminished tyramine activation of rhTA(1). Because TA(1) (EGFP-rhTA(1) chimera) was largely intracellular, conceivably the dopamine transporter can facilitate access of specific agonists to intracellular TA(1). rhTA(1) mRNA expression was detected in rhesus monkey substantia nigra, implying that TA(1) may be colocalized with the dopamine transporter in dopamine neurons. In summary, primate TA(1) receptors are direct targets of trace amines, amphetamine, and MDMA. These receptors could also be indirect targets of amphetamine, MDMA, and cocaine through modification of monoamine transporter function. Conceivably, rhTA(1) receptors may be located on pre- or postsynaptic membranes. Interference with the carrier function of monoamine transporters with a consequent rise of extracellular levels of trace amines could activate these receptors. The cloning of a highly homologous TA(1) from rhesus monkey and demonstration that rhTA(1) receptors are activated by drugs of abuse, indicate that nonhuman primates may serve to model physiological and pharmacological TA(1)-mediated responses in humans.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Amphetamine Sodium-dependent dopamine transporter Protein Humans YesNegative modulatorDetails Amphetamine Trace amine-associated receptor 1 Protein Humans YesAgonistDetails Dextroamphetamine Trace amine-associated receptor 1 Protein Humans UnknownAgonistDetails Metamfetamine Sodium-dependent dopamine transporter Protein Humans YesNegative modulatorDetails Metamfetamine Trace amine-associated receptor 1 Protein Humans YesAgonistDetails Propylhexedrine Trace amine-associated receptor 1 Protein Humans UnknownAgonistDetails