Comparison of effect of [D-Arg2,Sar4]-dermorphin (1-4) and morphine on mouse small intestinal transit and electrically evoked contraction of guinea pig ileum.

[D-Arg2,Sar4]-dermorphin (1-4) [DAS-DER (1-4)] was compared with morphine for the capacity to affect mouse gastrointestinal transit and electrically evoked contractions of the guinea pig ileum (GPI). A single subcutaneous injection with DAS-DER (1-4) and morphine dose-dependently inhibited gastrointestinal transit of charcoal in mice. DAS-DER (1-4) with ID50 of 0.053 mg/kg was 26 times more potent than morphine with ID50 of 1.38 mg/kg. The inhibitory effects of DAS-DER (1-4) and morphine were completely inhibited by pretreatment with 1 mg/kg naloxone, an opioid receptor antagonist. The GPI contraction was inhibited by DAS-DER (1-4) with an IC50 of 6.9 +/- 0.7 nM and morphine with an IC50 of 295.0 +/- 11.8 nM, respectively. These effects were also inhibited by preincubation with naloxone. Repeated subcutaneous injections of DAS-DER (1-4) and morphine to guinea pigs produced tolerance to the inhibitory effect on electrically evoked contractions of GPI. Moreover, a marked cross tolerance was seen in guinea pigs made tolerant to DAS-DER (1-4) or morphine. The present study indicates that pharmacological profiles of DAS-DER (1-4) as assayed by the gastrointestinal transit and stimulated contractions of the GPI were almost similar to that of morphine.