Differentiation of receptor subtypes by thermodynamic analysis: application to opioid delta receptors.
The temperature dependence of the dissociation constant for the interaction of an opioid delta 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 (delta G(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 delta receptor, and they further 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.
Wild
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KD
R.W. Johnson Pharmaceutical Research Institute, Spring House, PA 19477-0776.
Porreca
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F
Yamamura
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HI
Raffa
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RB
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002151:Calorimetry; D002462:Cell Membrane / Q000378:metabolism; D005910:Glioma; D006822:Hybrid Cells; D007700:Kinetics; D051379:Mice; D009447:Neuroblastoma; D011869:Radioligand Assay; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017465:Receptors, Opioid, delta / Q000737:chemistry / Q000145:classification* / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism*; D013816:Thermodynamics; D014407:Tumor Cells, Cultured
D011956:Receptors, Cell Surface; D017465:Receptors, Opioid, delta