Inhibition of motility in isolated horse small intestine is mediated by κ but not µ opioid receptors.

The effects of preferential µ (morphine), selective µ (fentanyl), selective κ (compound U69593) opioid receptor agonists, and nonselective (naloxone) and selective µ (naloxonazine) antagonists on equine small intestinal motility were evaluated in vitro. Samples of circular muscle from equine jejunum were placed in isolated organ baths and drug-induced modifications of both spontaneous and electrically evoked contractile activity were measured. None of the opioid agonists induced a significant change in spontaneous contractions. Fentanyl and U69593 reduced electrically induced contractions, whereas morphine reduced them only slightly. Naloxone competitively antagonised U69593, but both naloxone and naloxonazine were unable to counteract the inhibition of contractions induced by fentanyl. The inhibition of contractions shown by fentanyl is therefore probably not mediated by opioid receptors, but due to an anticholinergic activity of this drug. In summary, these data showed an inhibitory effect exerted by κ receptors on equine small intestinal motility, whereas the role of µ receptors seemed marginal and would need further characterisation.

Effects of nonselective and selective cyclooxygenase inhibitors on small intestinal motility in the horse.

We investigated the effects of nonselective cyclooxygenase (COX) inhibitors (indomethacin and flunixin meglumine) and selective COX-1 (SC-560) or COX-2 (celecoxib, DUP-398 and NS-697) inhibitors on horse small bowel motility in vitro. At this purpose, samples of equine ileum were put in isolated organ baths for the motility experiments. Nonselective COX inhibitors were devoid of major effects on motility, except for an inhibition of tonic contraction shown by flunixin meglumine. SC-560, selective COX-1 inhibitor, was devoid of significant effects on ileal motility. Selective COX-2 inhibitors reduced both tonic contraction and spontaneous phasic contractions, while prostaglandin (PG) receptor antagonists were uneffective. Some of the intestinal samples were submitted to histological investigation or reverse transcription-polymerase chain reaction (RT-PCR), which revealed the presence of an inflammation reaction and the presence of both COX isoforms mRNAs. Present data support the hypothesis that the effects of COX inhibitors on horse small intestinal motility are not linked to PG depletion.

Effects of oral curcumin on indomethacin-induced small intestinal damage in the rat.

Nonsteroidal anti-inflammatory drug (NSAID)-induced injury on gastrointestinal tract is well documented, and jejunal inflammation caused by indomethacin in rats is a broadly used experimental model of enteritis. We evaluated the effect of oral curcumin, a compound known to possess anti-inflammatory and anti-oxidant properties, on indomethacin-induced enteritis in the rat. Curcumin (50, 100, and 300 mg/kg) was given to rats by oral gavage 48, 24, and 1 h before enteritis was induced by intragastric administration of 20 mg/kg indomethacin. After 24 h, intestinal macroscopic lesions, myeloperoxidase activity and lipid peroxidation levels were assessed. Curcumin at the dose of 50 mg/kg was uneffective, while at the dose of 100 and 300 mg/kg significantly reduced macroscopic damage caused by indomethacin. By contrast, curcumin at all tested doses was unable to modify indomethacin-induced increases of myeloperoxidase and lipid peroxidation. Curcumin (100 and 300 mg/kg) significantly increased lipid peroxidation level in normal intestinal tissues of rats. Present data show that oral curcumin protects against macroscopic injury induced by indomethacin, leaving unaffected neutrophil infiltration and oxidative cell damage, thus suggesting that this beneficial effect is due to mechanisms not involving anti-inflammatory or antioxidant activities.