Differential effects of two kappa-opiate agonists, U-50,488H and U-69,593, on the binding of 3H-(3-MeHis2) thyrotropin-releasing hormone to rat spinal cord and amygdala membranes.

The effect of delta- and kappa-opiate receptor agonists on the binding of 3H-(3-MeHis2) thyrotropin-releasing hormone (3H-MeTRH) to membranes of the spinal cord and amygdala of male Sprague-Dawley rats was determined in an effort to further understand interactions between opiates and TRH receptors. The agonists used were D-Ala2-MePhe4-Gly-ol5-enkephalin (DAMGO, mu-receptor), cyclic D-penicillamine2-D-penicillamine5-enkephalin (DPDPE, delta-receptor), cyclic D-penicillamine2-L-penicillamine5-enkephalin (DPLPE, delta-receptor), D-Ala2-D-Leu5-enkephalin (delta-receptor), U-50,488H and U-69,593 (kappa-receptor). 3H-MeTRH bound to amygdala and spinal cord membranes at a single site with Bmax values of 35.7 +/- 5.4 and 15.8 +/- 2.6 fmol/mg protein, and Kd values of 6.3 +/- 1.1 and 5.2 +/- 0.7 nmol/l, respectively. The competition experiments were carried out at a concentration of 2 nmol/l 3H-MeTRH. The concentration of opiate ranged from 10(-9) to 10(-4) mol/l. DAMGO, DPDPE and DPLPE had no effect on the binding of 3H-MeTRH to amygdala or spinal cord membranes. The two highly selective kappa-agonists differed in their interaction with TRH receptors. Whereas U-69,593 did not modify the binding of 3H-MeTRH, U-50,488H significantly inhibited the binding of 3H-MeTRH to both spinal cord and amygdala membranes. U-50,488H has been found to be 10 times more potent than U-69,593 at the central kappa-opiate receptors and may explain their differential action at the TRH receptors. It is concluded that mu- and delta-opiate agonists do not interact with brain and spinal cord TRH receptors.(ABSTRACT TRUNCATED AT 250 WORDS)