Comparison of opioid receptor binding in horse, guinea pig, and rat cerebral cortex and cerebellum

OBJECTIVE: To compare the density and binding characteristics of opioid receptor subtypes in horse, rat, and guinea pig cerebral cortex and cerebellum. STUDY DESIGN: Prospective receptor binding study. ANIMALS: Whole brains were obtained from four neurologically normal adult horses during necropsy. Rat and guinea pig brains were obtained commercially. METHODS: The cerebellum and cerebral cortex were dissected from each brain, and tissue homogenates prepared. A radioligand binding technique with the highly selective ligands [(3)H]-DAMGO, [(3)H]-U69593, and [(3)H]-DPDPE was used to identify the mu- (mu), kappa- (kappa) and delta- (delta) opioid receptors, respectively. Competitive binding assays were performed with these ligands and varying concentrations of one of multiple unlabeled ligands. RESULTS: While there were marked species differences in relative densities of opioid receptors, all radioligands interacted with their binding sites with high, nanomolar affinity in both the cerebral cortex and cerebellum. In the horse cerebral cortex, the percentages of total opioid binding sites for the mu-, kappa- and delta-receptors were 71%, 14% and 15%, respectively. In the rat and guinea pig cerebral cortex, the corresponding values were 56% mu-, 4% kappa- and 40% delta-receptors, and 25% mu-, 37% kappa- and 38% delta-receptors, respectively. In horse and guinea pig cerebellum, the binding was 37% mu-, 59% kappa- and 4% delta-receptors, and 15% mu-, 76% kappa- and 10% delta-receptors, respectively. For competitive analysis, all competitors of the mu-, kappa- and delta-receptors completely displaced [(3)H]-DAMGO, [(3)H]-U69593, and [(3)H]-DPDPE and had inhibitory constants in the nanomolar range. CONCLUSION AND CLINICAL RELEVANCE: Horses used in this study had a greater density of mu-receptors in the cerebral cortex compared with rats and guinea pigs but without further characterization of the functional role of these receptors it is impossible to determine the clinical significance of these data.