Opiate receptor thermodynamics: Agonist and antagonist binding

The equilibrium thermodynamics of [³H]etorphine and [³H]diprenorphine binding to rat brain membranes were studied. In the absence of NaCl, the binding of [³H]etorphine was endothermic (ΔH° = +2.31 kcal/mol) and driven by a large increase in entropy (ΔH° = +51.8 e.u.). Under similar conditions, the binding of [³H]diprenorphine was exothermic (ΔH° = - 2.78 kcal/mol). In the presence of 100 mM Nacl, [³H]etorphine binding was relatively isothermic (ΔH° = +0.61 kcal/mol) and driven by a large increase in entropy ΔS° = +45.6 e.u.). NaCl significantly decreased both ΔH° (-2.78 to -7.48 kcal/mol) and ΔS° (33.0 to 18.5 e.u.) for [³H]diprenorphine binding. The data suggest that the agonist configuration of the opiate receptor exists in a more open and mobile (higher entropy) conformation than does the antagonist form of the receptor.