A possible mechanism in interaction of a partial agonist with beta-adrenoceptor in guinea-pig taenia caecum: effects of Gpp(NH)p on its two different binding sites.

The mechanisms of the actions of the beta-adrenergic partial agonist (befunolol) were studied in isolated guinea-pig taenia caecum. Befunolol, 2-acetyl-7-(2-hydroxy-3-isopropylaminopropoxy)benzofuran hydrochloride was found to be a typical partial agonist in guinea-pig taenia caecum. The pD2-value of befunolol was in agreement with its pKA-value obtained with photoaffinity labeling, but was different from its pA2-value against isoprenaline and pKI-value obtained from the inhibition of specific [3H]-dihydroalprenolol binding. The Scatchard plot of the specific [3H]-befunolol binding showed two affinity sites of the receptor in the absence of Gpp(NH)p, but the low affinity site was reduced while the high affinity site was not affected in the presence of Gpp(NH)p. The pKD-value of the high affinity site of befunolol was in agreement with its pA2-value, and the pKD-value of the low affinity site was in agreement with its pD2-value or pKA-value. These results suggest that the beta-adrenergic partial agonist may interact with two different sites: an agonist binding site and an antagonist binding site.