PMID- 15764732 OWN - NLM STAT- MEDLINE DCOM- 20050714 LR - 20220309 IS - 0022-3565 (Print) IS - 0022-3565 (Linking) VI - 313 IP - 3 DP - 2005 Jun TI - Primate trace amine receptor 1 modulation by the dopamine transporter. PG - 983-94 AB - 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. FAU - Miller, Gregory M AU - Miller GM AD - Division of Neurochemistry, New England Primate Research Center, Harvard Medical School, Southborough, MA 01772, USA. FAU - Verrico, Christopher D AU - Verrico CD FAU - Jassen, Amy AU - Jassen A FAU - Konar, Martha AU - Konar M FAU - Yang, Hong AU - Yang H FAU - Panas, Helen AU - Panas H FAU - Bahn, Mary AU - Bahn M FAU - Johnson, Ryan AU - Johnson R FAU - Madras, Bertha K AU - Madras BK LA - eng GR - DA06303/DA/NIDA NIH HHS/United States GR - RR00168/RR/NCRR NIH HHS/United States GR - P51 OD011103/OD/NIH HHS/United States GR - R01 DA006303/DA/NIDA NIH HHS/United States GR - DA15305/DA/NIDA NIH HHS/United States GR - K05 DA015305/DA/NIDA NIH HHS/United States GR - R01 DA011558/DA/NIDA NIH HHS/United States GR - P51 RR000168/RR/NCRR NIH HHS/United States GR - DA016606/DA/NIDA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, P.H.S. DEP - 20050311 PL - United States TA - J Pharmacol Exp Ther JT - The Journal of pharmacology and experimental therapeutics JID - 0376362 RN - 0 (Dopamine Plasma Membrane Transport Proteins) RN - 0 (Membrane Glycoproteins) RN - 0 (Membrane Transport Proteins) RN - 0 (Nerve Tissue Proteins) RN - 0 (Phenethylamines) RN - 0 (Receptors, G-Protein-Coupled) RN - 327C7L2BXQ (phenethylamine) RN - E0399OZS9N (Cyclic AMP) RN - I5Y540LHVR (Cocaine) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) RN - VTD58H1Z2X (Dopamine) RN - XMC8VP6RI2 (Trace amine-associated receptor 1) SB - IM MH - Amino Acid Sequence MH - Animals MH - Cells, Cultured MH - Cocaine/pharmacology MH - Cyclic AMP/biosynthesis MH - Dopamine/metabolism MH - Dopamine Plasma Membrane Transport Proteins MH - Humans MH - Macaca mulatta MH - Membrane Glycoproteins/*physiology MH - Membrane Transport Proteins/*physiology MH - Molecular Sequence Data MH - N-Methyl-3,4-methylenedioxyamphetamine/pharmacology MH - Nerve Tissue Proteins/*physiology MH - Phenethylamines/metabolism MH - Rats MH - Receptors, G-Protein-Coupled/*drug effects/physiology MH - Response Elements/physiology MH - Substantia Nigra/chemistry EDAT- 2005/03/15 09:00 MHDA- 2005/07/15 09:00 CRDT- 2005/03/15 09:00 PHST- 2005/03/15 09:00 [pubmed] PHST- 2005/07/15 09:00 [medline] PHST- 2005/03/15 09:00 [entrez] AID - jpet.105.084459 [pii] AID - 10.1124/jpet.105.084459 [doi] PST - ppublish SO - J Pharmacol Exp Ther. 2005 Jun;313(3):983-94. doi: 10.1124/jpet.105.084459. Epub 2005 Mar 11.