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 (delta Ho = +2.31 kcal/mol) and driven by a large increase in entropy (delta So = +51.8 e.u.). Under similar conditions, the binding of [3H]diprenorphine was exothermic (delta Ho = -2.78 kcal/mol). In the presence of 100 mM NaCl, [3H]etorphine binding was relatively isothermic (delta Ho = +0.61 kcal/mol) and driven by a large increase in entropy (delta So = +45.6 e.u.). NaCl significantly decreased both delta Ho (-2.78 to -7.48 kcal/mol) and delta So (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.