Thermodynamic parameters for [D-Pen2,5]enkephalin at [delta]-opioid receptors in the mouse isolated vas deferens

Abstract

Dissociation constants (KA) for [D-Pen2,5]enkephalin (DPDPE) inhibition of the electrically evoked twitch of the mouse isolated vas deferens preparations (MVD) were calculated at five temperatures (25, 30, 34, 37 and 40[deg]C). These values were determined from the equiactive concentrations obtained before (A) and after (A') partial irreversible blockade of a fraction of the receptor population by [beta]-chlornaltrexamine ([beta]-CNA) plotted as (1/A) against (1/A') where KA = slope - 1)/intercept. The values of KA tended to increase (approximately doubled) over this temperature range, indicating that the affinity of DPDPE for the opioid [delta] receptor is an inverse function of temperature. From these results, thermodynamic parameters were calculated from a Van 't Hoff plot of 1n(KA) against 1/T. The relative magnitudes of the change in enthapy ([Delta]H[deg]' = -6.67 kcal mol-1), the change in entropy ([Delta]S[deg]' = +0.009 kcal mol-1 [deg]K-1) and the change in free energy ([Delta]G[deg]' = -9.43 kcal mol-1) suggest that the interaction between DPDPE and the [delta]-opioid receptor in MVD is an exothermic exergonic reaction, predominantly enthalpy-driven and results in an increase in the entropy of the system.