Agonist-mediated conformational changes of beta-adrenoceptors could occur independent of functional coupling to Ns.
Agonist and antagonist binding characteristics of beta-adrenoceptors in turkey erythrocyte ghosts were determined at different temperatures ranging between 7 degrees C and 42 degrees C. [3H]-DHA saturation binding experiments revealed that the antagonist-receptor interaction is entropy-driven with a small enthalpic contribution. Isoproterenol/[3H]-DHA competition binding followed the law of mass action at all the investigated temperatures. The agonist-receptor interaction is enthalpy driven with a small unfavorable decrease in entropy. This is consistent with the agonist's ability to favor an endoenergetic transconformation of the receptors. Only part of the agonist-bound receptors can undergo functional coupling to the stimulatory component of the adenylate cyclase system (Ns). This coupling process is associated with "locking-in" of the agonist and becomes persistent in the presence of the alkylating reagent N-ethylmaleimide. The number of agonist/N-ethylmaleimide-sensitive sites (i.e. coupling-prone receptors) increases with the temperature until it reaches a plateau value of 50% between 27-32 degrees C. Qualitatively similar data were obtained for rat lung and turkey erythrocyte membranes. These observations suggest that the whole receptor population can undergo agonist-mediated conformational changes but that only part of them can couple to Ns.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D004082:Dihydroalprenolol / Q000378:metabolism; D004910:Erythrocyte Membrane / Q000378:metabolism; D005033:Ethylmaleimide / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D011487:Protein Conformation; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013816:Thermodynamics; D014422:Turkeys
D011943:Receptors, Adrenergic, beta; D004082:Dihydroalprenolol; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D005033:Ethylmaleimide