Thiol reactivity and the molecular individuality of alpha- and beta-adrenoreceptors in rat liver plasma membranes.
Whether or not alpha- and beta-adrenoreceptors are non-identical binding sites on the same protein is still an open question. We investigated the effects of sulfhydryl reagents and dithiothreitol on the binding of [3H]dihydroalprenolol and [3H]dihydroergocryptine to beta- and alpha-adrenoreceptors of rat liver plasma membranes. Dithiothreitol inhibited the binding of [3H]dihydroalprenolol to the beta-adrenoreceptor, whereas it had no effect on the specific binding of [3H]dihydroergocryptine to the alpha-adrenoreceptor. In contrast, mersalyl, a mercurial SH reagent, readily blocked the alpha-adrenoreceptor and, although to a lesser extent the beta-adrenoreceptor. The interaction of mersalyl with the alpha-adrenoreceptors was almost instantaneous. In contrast, under the same experimental conditions, the inactivation of the beta-adrenoreceptors was much slower (t 1/2 : 7 min). Finally, a marked difference in the accessibility of the SH groups to mersalyl was observed between the alpha- and beta-adrenoreceptors. The presence of 15 microM (-)-epinephrine or 1.5 microM phentolamine was sufficient to prevent the blockade of the alpha-adrenoreceptor by mersalyl, but inactivation of the beta-adrenoreceptor by mersalyl was not modified by 500 microM (-)-epinephrine and was only slightly decreased by 50 microM (-)-propranolol. Thus, the alpha- and beta-adrenoreceptors from rat liver plasma membranes exhibited biochemical differences which may be interpreted in favor of their molecular individuality.
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D004082:Dihydroalprenolol / Q000378:metabolism; D004088:Dihydroergotoxine / Q000378:metabolism; D004229:Dithiothreitol / Q000494:pharmacology; D005260:Female; D008099:Liver / Q000378:metabolism*; D008634:Mersalyl / Q000494:pharmacology; D051381:Rats; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013439:Sulfhydryl Reagents / Q000494:pharmacology
D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D013439:Sulfhydryl Reagents; D004088:Dihydroergotoxine; D008634:Mersalyl; D004082:Dihydroalprenolol; D004229:Dithiothreitol