DOWN-REGULATION OF BRAIN AND SPINAL-CORD KAPPA-OPIATE RECEPTORS IN SPONTANEOUSLY HYPERTENSIVE, WISTAR-KYOTO NORMOTENSIVE, AND SPRAGUE-DAWLEY RATS BY CHRONIC TREATMENT WITH U-50,488H

The effects of chronic administration of U-50,488H, a kappa-opiate receptor agonist, on the binding of [H-3]ethylketocyclazocine ([H-3]EKC) to kappa-opiate receptors on the cerebral cortical and spinal cord membranes of spontaneously hypertensive (SHR), Wistar-Kyoto normotensive (WKY), and Sprague-Dawley (SD) rats were determined. Age-matched (10 weeks old) male rats of each strain were injected twice daily for 7 days with either U-50,488H (25 mg/kg, i.p.) or its vehicle. On day 8, the rats were killed. The cerebral cortex and the spinal cord were isolated for binding studies. The systolic blood pressure and heart rate of SD and WKY rats did not differ but the blood pressure of SHR rats was higher than that of SD and WKY rats. The receptor density (B(max)) and apparent dissociation constant (K(d)) Values of [H-3]EKC binding to the spinal cord of WKY and SHR rats did not differ. However, the spinal cord of SD rats had higher B(max) and K(d) values than WKY or SHR rats. The cortex of the SD rats had a lower B(max) value than the other two strains. Treatment with U-50,488H decreased the B(max) value of [H-3]EKC in spinal cord of SD rats, increased the K(d) value in SHR rats, and had no effect in WKY rats. Decreases in the B(max) value were produced in the cortex of all strains of rats, but a greater effect was observed in WKY and SHR rats than in SD rats.