Differentiation of receptor subtypes by thermodynamic analysis: Application to opioid δ receptors

The temperature dependence of the dissociation constant for the interaction of an opioid δ selective ligand and its receptor was evaluated in three tissues. The change in free energy of this interaction was similar in mouse brain, mouse spinal cord, and NG 108-15 mouse neuroblastoma-rat glioma hybrid cells (ΔG(o)' = -13.44, -13.34, and -13.66 kcal · mol^-1, respectively). However, the reaction was endothermic and occurred with an increase in entropy in mouse brain and NG 108-15 cells, but it was exothermic and occurred with a negligible change in entropy in mouse spinal cord. These data are consistent with the existence of multiple subtypes of opioid δ receptor, and they further suggest that the opioid δ receptor recently cloned from the NG 108-15 cell line is of the brain subtype. Subtypes of opioid δ receptors may mediate analgesia, but not side-effects, of opiates and thus could be targets for future drug design.