It has been suggested that there is a link between epinephrine synthesis and the development of β2-adrenoceptor–mediated effects. In this article, the study aim was to characterize β-adrenoceptor–mediated relaxation and facilitation of norepinephrine release in the aorta of phenylethanolamine-N-methyltransferase-knockout (Pnmt-KO) mice. Epinephrine is absent in Pnmt-KO mice. In isolated aortic ring studies, the potency and the maximal effect of the β2-adrenoceptor agonist terbutaline were lower in Pnmt-KO than in wild-type (WT) mice. The selective β2-adrenoceptor antagonist, ICI-118551 [(±)-erythro-(S*,S*)-1-[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol hydrochloride], antagonized the relaxation caused by terbutaline in WT mice, but not in Pnmt-KO mice. β2-Adrenoceptor protein density was decreased in membrane aorta homogenates of Pnmt-KO mice, and this finding was supported by immunofluorescence confocal microscopy. In the absence of epinephrine, β2-adrenoceptor protein density was decreased in aorta cell membranes, thus potentially hindering its functional activity.
See article at J Pharmacol Exp Ther 2014, 351:243–249.
- Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics