| Abstrakt: |
The compound FM24, 1-(2-exo-bicyclo(2,2, 1]hept-2-ylphenoxy)-3-[(1-methyl-ethyl)amino]-2-propanol, hydrochloride, inhibited isoproterenol-dependent adenylate cyclase from rat liver plasma membranes, while it had no effect on the basal, fluoride-, Gpp(NH)p-, and glucagon-dependent cyclase activities. FM24also blocked the specific binding of (−)[3H]dihydroalprenolol to the rat liver β-adrenoreceptors. The inhibition was of the non-competitive type and could not be reversed by extensive washing, unlike the competitive, reversible, inhibition caused by propranolol. Preincubation with either propranolol or isoproterenol protected the binding sites and adenylate cyclase activity against inactivation by FM24. These findings suggest that FM24behaves as a non-dissociable or a very slowly reversible β-receptor antagonist. This may be due to the hydrophobic nature of the molecule, and is supported by experiments done with several structural analogs of FM24. |
