Thermodynamics of agonist and antagonist binding to the alpha 1-adrenoceptor studied using [125I]BE 2254

The thermodynamics of binding of [125I]BE 2254 to the alpha 1-adrenoceptor in guinea pig brain membranes have been investigated at four different temperatures between 0 and 37 degrees C. The affinity and binding capacity of the radioligand did not vary with temperature. Thus, the change in enthalpy upon binding was close to zero whereas the change in entropy was large and positive (delta S degrees approximately 45 cal/mol-deg). In addition, [125I]BE 2254 has been used as a reporter ligand to probe the thermodynamics of the interaction of a variety of alpha-adrenoceptor agonists and antagonists with the alpha 1-adrenoceptor. Binding of all ligands was associated with large positive changes in entropy (delta S degrees between 18 and 48 cal/mol-deg) and little, or no, change in enthalpy, a finding that provides no convincing evidence for conformational rearrangement of alpha 1-adrenoceptors upon ligand binding.