Purpose: The rise in consumption of dietary supplements containing the trace amines p-tyramine, p-synephrine and p-octopamine has been associated with cardiovascular side effects. Since renal blood flow plays an important role in blood pressure regulation, this study investigated the mechanisms of action of these trace amines on isolated porcine renal arteries.
Main Methods: Contractile responses to amines were investigated in noradrenaline-depleted rings of porcine main renal arteries in the absence and presence of the α-adrenoceptor antagonist, prazosin (1 μM), β-adrenoceptor antagonist, propranolol (1 μM), or the trace amine-associated receptor (TAAR-1) antagonist, EPPTB (RO-5212773; 100 nM or 100 μM).
Key Findings: All three amines induced constrictor responses of similar magnitude and potency. However, their mechanisms of action on the renal artery appeared to differ. Depleting endogenous noradrenaline stores significantly reduced maximum responses to tyramine and synephrine, but less for octopamine. When direct responses were examined after depleting tissues of noradrenaline, responses to synephrine and octopamine, but not tyramine, were reduced in the presence of prazosin(1 μM) and potentiated in the presence of propranolol (1 μM) or L-NNA (100 μM). Generally, vasoconstrictor responses remaining after noradrenaline-depletion and α-adrenoceptor blockade were not affected by the TAAR-1 antagonist EPPTB (0.1-100 μM), although responses to low concentration of synephrine and octopamine were enhanced by this antagonist.
Significance: Tyramine appears to mediate constriction of the renal artery mainly via an indirect sympathomimetic mechanism, whereas synephrine and octopamine exert additional direct effects on α-adrenoceptors and possibly contractile TAAR (not TAAR-1). The two amines also activate simultaneous inhibitory responses via β-adrenoceptors, TAAR-1 and nitric oxide release.
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http://dx.doi.org/10.1016/j.lfs.2021.119532 | DOI Listing |
ACS Synth Biol
June 2024
State Key Laboratory of Materials-Oriented Chemical Engineering, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 211816, People's Republic of China.
Sci Rep
December 2022
Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo, 11566, Egypt.
Biomolecules
November 2022
UCIBIO, REQUIMTE, Laboratory of Toxicology, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
Biomolecules
October 2022
Institute of Clinical Pharmacology, University Medical Center Göttingen, D-37075 Göttingen, Germany.
Stereoselectivity is well known and very pronounced in drug metabolism and receptor binding. However, much less is known about stereoselectivity in drug membrane transport. Here, we characterized the stereoselective cell uptake of chiral phenylethylamine derivatives by human monoamine transporters (NET, DAT, and SERT) and organic cation transporters (OCT1, OCT2, and OCT3).
View Article and Find Full Text PDFNutrients
July 2022
Department of Plastic Surgery, CHU Rangueil, 31059 Toulouse, France.
Dietary amines have been the subject of a novel interest in nutrition since the discovery of trace amine-associated receptors (TAARs), especially TAAR-1, which recognizes tyramine, phenethylamine, tryptamine, octopamine, -methyltyramine (NMT), synephrine, amphetamine and related derivatives. Alongside the psychostimulant properties of TAAR-1 ligands, it is their ephedrine-like action on weight loss that drives their current consumption via dietary supplements advertised for 'fat-burning' properties. Among these trace amines, tyramine has recently been described, at high doses, to exhibit an antilipolytic action and activation of glucose transport in human adipocytes, i.
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