DIFFERENTIATION OF RECEPTOR SUBTYPES BY THERMODYNAMIC ANALYSIS - APPLICATION TO OPIOID-DELTA RECEPTORS

The temperature dependence of the dissociation constant for the intera ction of an opioid delta selective ligand and its receptor was evaluat ed in three tissues, The change in free energy of this interaction was similar in mouse brain, mouse spinal cord, and NG 108-15 mouse neurob lastoma-rat glioma hybrid cells (Delta G degrees' = -13.44, -13.34, an d -13.66 kcal.mol(-1), respectively), However, the reaction was endoth er mic and occurred with an increase in entropy in mouse brain and NG 108-15 cells, but it was exothermic and occurred with a negligible cha nge in entropy in mouse spinal cord. These data are consistent with th e existence of multiple subtypes of opioid delta receptor, and they fu rther suggest that the opioid delta receptor recently cloned from the NG 108-15 cell line is of the brain subtype, Subtypes of opioid delta receptors may mediate analgesia, but not side-effects, of opiates and thus could be targets for future drug design.