Guinea-pigs treated with beta-endorphin fragments DT gamma E and DE gamma E exhibit reduced morphine inhibition of electrically-induced contractions

Capasso, Anna and Alberto Loizzo: Guinea-pigs treated with beta-endorphin f ragments DT gamma E and DE gamma E exhibit reduced morphine inhibition of t he electrically-induced contractions. Frog. Neuro-Psychopharmacol. & Biol. Psychiat. 2000, 24, pp. 51-59. (C)1999 Elsevier Science Inc. 1. The effect exerted by two gamma-endorphin derivatives (DT gamma E and DE gamma E) was investigated on morphine-induced inhibition on the electrical ly contractions of guinea pig ileum in vitro. 2. Morphine (1x10(-8)-5x 10(- 8)-1x10(-7) M) dose dependently and significantly reduced the E.C. of guine a pig ileum, IC50=6.5x10(-8) M (Confidence limits:3.7x10(-8)-9.1x10(-8)). 3. DT gamma E and DE gamma E per se (1x10(-6) 5x10(-6)-1x10(-5) M) did not modify significantly the E.C. of guinea pig ileum. Furthermore, DT gamma E or DE gamma E injection 10-30-60 min before morphine, did not affect the in hibitory effect of morphine on the EC. of guinea pig ileum. 4. By contrast, ilea from guinea-pigs treated for 4 days with DT gamma E or DE gamma E (1 mg/Kg/i.p.) resulted less sensitive ro the inhibitory effect of morphine, IC50=8.3x10(-7) M (Confidence limits: 1.4x10(-6)-3.5x10(-7)) for DT gamma E and IC50=7.7x10(-7) M (Confidence limits: 2.7x10(-6)-8.7x10( -7)) for DE gamma E. 5. Our results indicate that chronic treatment of guinea pigs with DT gamma E;or DE gamma E induces a significant reduction of the inhibitory effect o f morphine on the E.C. of guinea-pig ileum thus confirming an important fun ctional interaction between gamma-endorphin derivatives and opioid system.