Influence of group selective reagents in tissues containing alpha- and beta-adrenoceptors.
N-ethylmaleimide which is known to react irreversibly with free -SH groups of protein when incubated with rabbit aorta (alpha-adrenoreceptor) or atria (beta-adrenoreceptor) markedly depressed the dose-response curves of norepinephrine isomers in the aorta but not in atria. Dithiothreitol, a reagent which reduces S-S linkages caused a parallel shift of the dose-response curves of both isomers to an equal degree in aorta. However, in atria the reagent drastically and selectively reduced the maximal effects of (+)-norepinephrine and dopamine. This selective alteration of the (+)-isomer by the reagent probably reflects the conformational changes at the beta-adrenoreceptor. The concentrations of N-ethylmaleimide and dithiothreitol required to alter the activity of norepinephrine isomers was higher for atria than for aorta. It may be that alpha-adrenoreceptors are more susceptible than the beta-adrenoreceptors on the -SH group selective reagents. In the highest concentration tested, two other reagents 2,4-dimethoxybenzylamine and N-acetylimidazole, did not influence the activity of the steroisomers on aorta. In the presence of dithiothreitol, the pharmacologic effects of a nonadrenoreceptor stimulant drug, histamine was potentiated on aorta (H1) and not on atria (H2). Results are discussed in the light of similarity and dissimilarity of adrenoreceptors as reflected by the group selective reagents and the stereoisomers.
D000818:Animals; D001011:Aorta / Q000187:drug effects; D001596:Benzylamines / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005033:Ethylmaleimide / Q000494:pharmacology; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D009638:Norepinephrine / Q000494:pharmacology; D011817:Rabbits; D011941:Receptors, Adrenergic / Q000187:drug effects*; D013237:Stereoisomerism; D013439:Sulfhydryl Reagents / Q000494:pharmacology*
D001596:Benzylamines; D007093:Imidazoles; D011941:Receptors, Adrenergic; D013439:Sulfhydryl Reagents; C012292:2,4-dimethoxybenzylamine; D005033:Ethylmaleimide; D004229:Dithiothreitol; D009638:Norepinephrine