[Effect of pH changes on the binding of agonists and antagonists to the adrenergic beta receptor].
The effect of pH on [3H]-DHA specific binding and its displacement by various nonlabeled ligands from beta-adrenoreceptors was examined in sarcolemmal membranes from canine hearts. At low pH (6.69) the affinity of beta-adrenoreceptors for agonists is lower than at pH 7.65, causing a 1.50-fold increase in the inhibition constant (KI) of both (-) noradrenaline and (-) isoprenaline. The change in the affinity was attenuated by adding 300 microM GTP to the reaction medium. Low pH neither affected the affinity of antagonists ((-) dihydroalprenolol, (+/- ) alprenolol, ( +/- ) propranolol) for adrenoreceptors nor the number of binding sites determined by [3H]-DHA binding assays. The effect of pH suggests that H+ induces the formation of a low affinity state of beta-adrenoreceptors for agonists. This H+-dependent mechanism may be capable of regulating the process by which agonists stimulate adenyl cyclase.
Gende
O A
OA
Camilión de Hurtado
M C
MC
Cingolani
H E
HE
D000136:Acid-Base Equilibrium; D000318:Adrenergic beta-Agonists / Q000378:metabolism*; D000319:Adrenergic beta-Antagonists / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D004082:Dihydroalprenolol / Q000378:metabolism; D004285:Dogs; D006863:Hydrogen-Ion Concentration; D007545:Isoproterenol / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D004082:Dihydroalprenolol; D007545:Isoproterenol; D009638:Norepinephrine
Efecto de las variaciones del pH sobre la unión de agonistas y antagonistas al receptor beta adrenérgico.