Dissociation constants (K(B)) for naloxone inhibition of the actions of DPDPE in the mouse isolated vas deferens preparation (inhibition of electrically induced twitch) were determined at five temperatures ranging between 25 and 40°C. The values of K(B) tended to increase with temperature over the range examined, indicating that the affinity of naloxone for the opioid δ receptor is an inverse function of temperature. Using these data, the thermodynamic quantities ΔG°' (change in free energy), ΔH°' (change in enthalpy) and ΔS°' (change in entropy) were calculated from a van't Hoff plot of In (K(B)) against 1/T. The thermodynamic quantities determined in this study in vivo (ΔG°' = -10.59 kcal mol-1, ΔH°' = -15.73 kcal mol- 1 and ΔS°' = -0.0168 kcal mol-1 °K-1) are consistent with data reported from radioligand binding studies in vitro and suggest that the interaction between naloxone and the opioid δ receptor in the mouse isolated vas deferens is enthalpy driven. These data represent the first evaluation of the thermodynamics of opioid antagonist/receptor interaction in a physiological assay.
|Original language||English (US)|
|Number of pages||6|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - Dec 1 1992|
ASJC Scopus subject areas
- Molecular Medicine