Stereoselective effect of beta-endorphin on the production of analgesia and the spinal release of met-enkephalin in rats.

The author has previously reported that i.c.v. beta-endorphin increases the release of immunoreactive Met-enkephalin from the spinal cord. The present studies were conducted to study the effects of beta-endorphin and its position 5 amino acid-substituted analogs on the production of analgesia and the spinal release of Met-enkephalin in rats. Analgesia was measured by tail-flick test in conscious rats, and the release of Met-enkephalin from the spinal cord was studied in urethane-anesthetized rats using a technique of spinal superfusion. beta-Endorphin (0.8-40 micrograms i.c.v.) inhibited the tail-flick response in a dose-related manner, whereas D-Met5-beta-endorphin, even at the highest dose, 40 micrograms, was unable to inhibit the tail-flick response. L- and D-Leu5-beta-endorphin inhibited the tail-flick response only at high doses, with the D-isomer being slightly more potent than the L-isomer. Human beta-endorphin (0.8-16 micrograms i.c.v.) caused a dose-dependent increase of Met-enkephalin release from the spinal cord, whereas D-Met5-beta-endorphin, even at a high dose (16 micrograms), showed no release of Met-enkephalin. Leu5-beta-endorphin and D-Leu5-beta-endorphin showed little or no release of Met-enkephalin. The results indicate that beta-endorphin shows stereoselectivity on the production of analgesia and the release of Met-enkephalin.