Identification of trace-amine-associated receptors (TAAR) in the rat aorta and their role in vasoconstriction by β-phenylethylamine.
Trace amines including tyramine and β-phenylethylamine (β-PEA) increase blood pressure and cause vasoconstriction which is attributed to indirect sympathomimetic actions. However, there is evidence that they may also have non-sympathomimetic mechanisms. This study examined whether β-PEA causes vasoconstriction of rat aorta by a sympathomimetic action or through the recently described trace-amine-associated receptors (TAAR). Concentration-response curves (CRCs) for β-PEA were constructed either cumulatively or non-cumulatively in rat isolated aortic rings. TAAR-1 and TAAR-4 protein expression was determined in rat aorta by Western blotting and TAAR-1 mRNA by reverse transcriptase polymerase chain reaction (RT-PCR). β-PEA caused concentration-related constriction of rat aorta. The contractions were unaffected by endothelium removal or the nitric oxide synthase inhibitor, N(ω)-nitro-L-arginine methyl ester (L-NAME, 100 μM) or the cyclooxygenase inhibitor, indomethacin (10 μM). Non-cumulative CRCs showed greater contractions and sensitivity to β-PEA than cumulative. The α(1)-adrenoceptor antagonist, prazosin, failed to inhibit either curve. The β-adrenoceptor antagonist, propranolol, the adrenergic neuronal transport inhibitor, cocaine, and the monoamine oxidase inhibitor, pargyline, also failed to alter the CRC. In the combined presence of prazosin, cocaine, pargyline, and the selective β(2)-adrenoceptor antagonist, ICI-118,551, the trace amine contractile potency order was tryptamine > β-PEA > octopamine > D: -amphetamine > tyramine. Western blotting and RT-PCR revealed the presence of TAAR-1 in rat aorta, but TAAR-4 was poorly expressed. Vasoconstriction of rat aorta by β-PEA appears not to be an indirect sympathomimetic action. The presence of TAAR-1 suggests that vasoconstriction may be via these receptors; however, the potency order differed from that reported for transfected cells expressing rat TAAR-1.
Fehler
Martina
M
Welsh School of Pharmacy, Cardiff University, Cardiff, South Wales, CF10 3NB, UK.
Broadley
Kenneth J
KJ
Ford
William R
WR
Kidd
Emma J
EJ
D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D010627:Phenethylamines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014661:Vasoconstriction / Q000187:drug effects*; D000095383:Trace Amine-Associated Receptors
D010627:Phenethylamines; D043562:Receptors, G-Protein-Coupled; D000095383:Trace Amine-Associated Receptors; C029261:phenethylamine
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