Guinea-pigs treated with beta-endorphin fragments DTgammaE and DEgammaE exhibit reduced morphine inhibition of electrically-induced contractions.

The effect exerted by two gamma-endorphin derivatives (DTgammaE and DEgammaE) was investigated on morphine-induced inhibition on the electrically contractions of guinea pig ileum in vitro. Morphine (1x10(-8)-5x10(-8)-1x10(-7) M) dose dependently and significantly reduced the E.C. of guinea pig ileum, IC50=6.5x10(-8) M (Confidence limits: 3.7x10(-8)-9.1x10(-8)). DTgammaE and DEgammaEper se (1x10(-6)-5x10(-6)-1x10(-5) M) did not modify significantly the E.C. of guinea pig ileum. Furthermore, DTgammaE or DEgammaE injection 10-30-60 min before morphine, did not affect the inhibitory effect of morphine on the E.C. of guinea pig ileum. By contrast, ilea from guinea-pigs treated for 4 days with DTgammaE or DEgammaE (1 mg/Kg/i.p.) resulted less sensitive to the inhibitory effect of morphine, IC50=8.3x10(-7) M (Confidence limits: 1.4x10(-6)-3.5x10(-7)) for DTgammaE and IC50=7.7x10(-7) M (Confidence limits: 2.7x10(-6)-8.7x10(-7)) for DEgammaE. Our results indicate that chronic treatment of guinea pigs with DTgammaE or DEgammaE induces a significant reduction of the inhibitory effect of morphine on the E.C. of guinea-pig ileum thus confirming an important functional interaction between gamma-endorphin derivatives and opioid system.