The aim of the study was to evaluate the effects of centrally and peripherally acting
opioid antagonists such as
naloxone (NX),
naloxone methiodide, (+)-
naloxone [(+)NX], (-)-a-5,9-diethyl-2'-hydroxy-2 (3-furylmethyl)-6,7-benzomorphan and
naltrindole on gastrointestinal (GI) transit in mice with
diarrhea associated with intestinal
inflammation. Our hypothesis was that
diarrhea/
inflammation could induce a release of endogenous
opioid peptides that would play an inhibitory role in the physiological response to intestinal
inflammation; the administration of
opioid antagonists would uncover the effects of the endogenous
opioid peptides on the gut.
Diarrhea associated with
inflammation was induced in mice by administration of
croton oil (CO) although control animals received saline (SS); GI transit was evaluated with a
charcoal meal. The i.p. administration of 0.1 mg/kg NX or NXME, induced a significant increase in GI transit in CO but not in SS-treated animals (P < .005). At the same dose, (+)NX had no effect either in CO or SS groups. The kappa antagonist
MR-2266 (1 and 3 mg/kg) had no effect on GI transit in SS or CO animals. However, the delta antagonist
naltrindole (3 mg/kg), caused a small but significant (P < .01) increase in GI transit in the CO group. These results suggest that endogenous
opioid peptides are released in CO-treated animals and exert an inhibitory control of intestinal motility, which is unmasked by
opioid antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)