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.
Nakata
N
N
Department of Pharmacology, Tohoku College of Pharmacy, Sendai, Japan.
Sakurada
S
S
Sakurada
T
T
Tan-No
K
K
Kisara
K
K
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D004558:Electric Stimulation; D005772:Gastrointestinal Transit / Q000187:drug effects*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009842:Oligopeptides / Q000494:pharmacology*
D000701:Analgesics, Opioid; D009842:Oligopeptides; C047133:dermorphin (1-4), Arg(2)-Sar(4)-; D009020:Morphine