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.
D000698:Analgesia; D000818:Animals; D003429:Cross Reactions; D004305:Dose-Response Relationship, Drug; D004723:Endorphins / Q000494:pharmacology*; D004744:Enkephalin, Methionine / Q000378:metabolism*; D007106:Immune Sera; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism*; D013237:Stereoisomerism; D001615:beta-Endorphin / Q000031:analogs & derivatives
D004723:Endorphins; D007106:Immune Sera; D011957:Receptors, Opioid; C045185:beta-endorphin, Leu(5)-; C043460:epsilon receptor; D004744:Enkephalin, Methionine; D001615:beta-Endorphin