PERIPHERAL EFFECTS OF OPIOIDS IN A MODEL OF INTESTINAL INFLAMMATION IN MICE

The study evaluates the peripheral component of the antitransit effect s of opioids during acute intestinal inflammation induced by the intra gastric administration of croton oil (GO) in mice. Gastrointestinal tr ansit was measured 3 h after CO or saline (SS) administration with a c harcoal meal. In both groups, the effects of mixed (morphine, fentanyl , U-50488H) and peripherally acting (N-methylmorphine, PL017, ICI-2044 48) opioids and their antagonism by naloxone and naloxone methiodide w ere established. During inflammation, the potencies of morphine and N- methylmorphine increased 3 times, and those of fentanyl and PLO 17, 1. 9 times. The effects were reversed by naloxone (0.1 mg/kg) and naloxon e methiodide (0.3 mg/kg). No dose-response relationships could be elic ited with U-50488H or ICI-204448, and their antitransit effects were a nalogous in SS- and CO-treated animals. These results show that during inflammation the enhanced antitransit effects of opioids are primaril y mediated by interaction with opioid receptors located at peripheral sites. In addition, inflammation of the gut seems to induce a sensitiz ation of mu- but not kappa-opioid receptors.