CHARACTERIZATION OF THE VASORELAXANT ACTIVITY OF TYRAMINE AND OTHER PHENYLETHYLAMINES IN RAT AORTA

We recently reported that tyramine caused concentration-dependent rela xation of rat aorta, which was endothelium independent and was not exe rted via alpha(1)-adrenoceptors (AR), alpha(2)AR, beta(1)AR, beta(2)AR , or receptors for 5-hydroxytryptamine, histamine, and adenosine. The present studies were done on endothelium-denuded strips to determine s tructure - vasorelaxant activity after blockade of beta AR by proprano lol plus irreversible blockade of alpha(1)AR with benextramine. Vasore laxation under these conditions was limited to noncatecholamines, and their vasorelaxant potencies were methoxyphenamine > tyramine > p-hydr oxyephedrine > L-amphetamine > L-ephedrine > phenylethylamine > syneph rine > methoxamine > octopamine. beta(3)AR agonists (BRL 37344 and CGP 12177A) did not produce vasorelaxation, although tyramine could compe te for cyanopindolol binding to murine L cells expressing human beta(2 )AR or beta(3)AR. There was no significant specific binding of [H-3]ty ramine to aortic membrane preparations after the inhibition of monamin e oxidase. Yohimbine, which has a high affinity for Drosophila tyramin e receptors, also caused dose-dependent vasorelaxation like tyramine. It is concluded that tyramine and several other phenylethylamines prod uce relaxation of rat aorta, which does not involve any of the known a drenoceptors but may be exerted via novel tyramine receptors.