Modulation of Resistance Artery Tone by the Trace Amine β-Phenylethylamine: Dual Indirect Sympathomimetic and α1-Adrenoceptor Blocking Actions
| Autor: | Julie Sigurdson, Deepak Narang, Andrew Holt, Stephanie E. Lunn, Frances Plane, Margaret D. Lalies, Rhys I. Beaudry, Paul M Kerr, Alan L. Hudson, Peter E. Light |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Sympathetic Nervous System Monoamine oxidase Rauwolscine Prostaglandin Vasodilation In Vitro Techniques Pharmacology Methoxamine Rats Sprague-Dawley chemistry.chemical_compound Receptors Adrenergic alpha-1 Phenethylamines medicine Animals Phenylephrine Trace amine Yohimbine food and beverages Adrenergic alpha-2 Receptor Antagonists Mesenteric Arteries Rats chemistry Biochemistry Vasoconstriction Adrenergic alpha-1 Receptor Antagonists Molecular Medicine Adrenergic alpha-1 Receptor Agonists Endothelium Vascular medicine.symptom Protein Binding medicine.drug |
| Zdroj: | Journal of Pharmacology and Experimental Therapeutics. 351:164-171 |
| ISSN: | 1521-0103 0022-3565 |
| Popis: | The trace amine β-phenylethylamine (PEA) is normally present in the body at low nanomolar concentrations but can reach micromolar levels after ingestion of drugs that inhibit monoamine oxidase and primary amine oxidase. In vivo, PEA elicits a robust pressor response, but there is no consensus regarding the underlying mechanism, with both vasodilation and constriction reported in isolated blood vessels. Using functional and biochemical approaches, we found that at low micromolar concentrations PEA (1-30 μM) enhanced nerve-evoked vasoconstriction in the perfused rat mesenteric bed but at a higher concentration (100 μM) significantly inhibited these responses. The α2-adrenoceptor antagonist rauwolscine (1 µM) also enhanced nerve-mediated vasoconstriction, but in the presence of both rauwolscine (1 µM) and PEA (30 µM) together, nerve-evoked responses were initially potentiated and then showed time-dependent rundown. PEA (10 and 100 μM) significantly increased noradrenaline outflow from the mesenteric bed as determined by high-pressure liquid chromatography coupled with electrochemical detection. In isolated endothelium-denuded arterial segments, PEA (1 µM to 1 mM) caused concentration-dependent reversal of tone elicited by the α1-adrenoceptor agonists noradrenaline (EC50 51.69 ± 10.8 μM; n = 5), methoxamine (EC50 68.21 ± 1.70 μM; n = 5), and phenylephrine (EC50 67.74 ± 16.72 μM; n = 5) but was ineffective against tone induced by prostaglandin F2 α or U46619 (9,11-dideoxy-9α,11α-methanoepoxyprostaglandin F2 α). In rat brain homogenates, PEA displaced binding of both [(3)H]prazosin (Ki ≈ 25 μM) and [(3)H]rauwolscine (Ki ≈ 1.2 μM), ligands for α1- and α2-adrenoceptors, respectively. These data provide the first demonstration that dual indirect sympathomimetic and α1-adrenoceptor blocking actions underlie the vascular effects of PEA in resistance arteries. |
| Databáze: | OpenAIRE |
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