A pharmacologically pre-contracted smooth muscle bowel model for the study of highly-potent opioid receptor agonists and antagonists

Isolated organ models are a versatile tool for pharmacological and toxicological research. Small bowel has been used to assess the inhibition of smooth muscle contraction by opioids. In the present study, we set out to establish a pharmacologically stimulated rat bowel model. The effects of carfentanil, remifentanil and the new synthetic opioid U-48800 and their respective antagonists naloxone, nalmefene and naltrexone were studied in a small bowel model in rats. The IC50 values of the tested opioids were as follows: carfentanil (IC50 = 0.02 mu mol/L, CI 0.02-0.03 mu mol/L) >> remifentanil (IC50 = 0.51 mu mol/L, CI 0.40-0.66 mu mol/L) >> U-48800 (IC50 = 1.36 mu mol/L, CI 1.20-1.54 mu mol/L). The administration of the opioid receptor antagonists naloxone, naltrexone and nalmefene led to progressive, parallel rightward shifts of the dose-response curves. Naltrexone was most potent in antagonizing the effects of U-48800, whereas naltrexone and nalmefene were most effective in antagonizing the effects of carfentanil. In summary, the current model seems to be a robust tool to study opioid effects in a small bowel model without the necessity of using electrical stimulation.

Automated summary

Isolated organ models are valuable for studying the effects of opioids, and in this study, a rat small bowel model was established to evaluate the effects of carfentanil, remifentanil, and U-48800. The IC50 values of these opioids were determined, and the administration of antagonist drugs shifted the dose-response curves. This model provides a robust alternative to electrical stimulation for studying opioid effects in the small bowel.