COMPARISON OF EFFECT OF [D-ARG(2),SAR(4)]-DERMORPHIN-(1-4) AND MORPHINE ON MOUSE SMALL-INTESTINAL TRANSIT AND ELECTRICALLY-EVOKED CONTRACTION OF GUINEA-PIG ILEUM

[D-Arg(2),Sar(4)]-dermorphin (1-4) [DAS-DER (1-4)] was compared with m orphine for the capacity to affect mouse gastrointestinal transit and electrically evoked contractions of the guinea pig ileum (GPI). A sing le subcutaneous injection with DAS-DER (1-4) and morphine dose-depende ntly inhibited gastrointestinal transit of charcoal in mice. DAS-DER ( 1-4),vith ID50 of 0.053 mg/kg was 26 rimes more potent than morphine w ith ID50 of 1.38 mg/kg. The inhibitory effects of DAS-DER (1-4) and mo rphine were completely inhibited by pretreatment with I 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. Repented subcutaneous injections of D AS-DER (1-4) and morphine to guinea pigs produced tolerance to the inh ibitory effect on electrically evoked contractions of GPI. Moreover a marked cross tolerance was seen in guinea pigs made tolerant to DAS-DE R (1-4) or morphine. The present study indicates that pharmacological profiles of DAS-DER (1-4) as assayed by the gastrointestinal transit a nd stimulated contractions of the GPI were almost similar to that of m orphine. (C) 1998 Prous Science. All rights reserved.