Related Experiment Videos
Opioid receptor agonists in the rabbit colon: comparison of in vivo and in vitro studies
Abstract:
Myoelectrical activity was recorded in the proximal and distal colon of rabbits using chronically implanted electrodes. The motility in both the proximal and distal colon was inhibited by the intravenous (IV) administration of the following opioid agonists for mu receptors: morphine and fentanyl, kappa receptors: ethylketazocine (EKC) and U 50 488 H, and delta receptors: D-Ala2 D-Leu5-enkephalin (DADLE) and D-Ser2 Leu-enkephalin-Thr6 (DSLET). In contrast, the myoelectric activity in the distal colon was increased during the infusion of an endogenous kappa opioid agonist, dynorphin (DYN). All of these effects were prevented by naloxone pretreatment. During in vitro studies using extraluminal force transducers, fentanyl, U 50 488 H and DSLET inhibited spontaneous contractions of the proximal colon, but U 50 488 H and DSLET caused a substantial increase in the motility of the distal colon. The observed motor responses in the proximal and distal colon following opioid agonist administration indicate that the control of these two intestinal segments may be different. It is suggested that the stimulatory effect of dynorphin on the distal colon is peripherally-mediated while inhibition of the whole colon by opioid agonists regardless of subtypes seems to be centrally-mediated.
Insights
Opioid agonists generally inhibit rabbit colon motility, but dynorphin stimulates the distal colon. These differing responses suggest distinct central and peripheral control mechanisms for proximal and distal colon segments.
Area of Science:
- Gastroenterology
- Pharmacology
- Neuroscience
Background:
- Opioid receptors are present throughout the gastrointestinal tract.
- Opioid administration can significantly impact gut motility.
Purpose of the Study:
- To investigate the differential effects of various opioid receptor agonists on proximal and distal colon motility in rabbits.
- To explore the potential central versus peripheral mediation of these opioid-induced motor responses.
Main Methods:
- Chronic electrode implantation in rabbits for in vivo myoelectric activity recording.
- Intravenous administration of opioid agonists (morphine, fentanyl, ethylketazocine, U 50 488 H, DADLE, DSLET, dynorphin).
- In vitro studies using force transducers to measure spontaneous colonic contractions.
Main Results:
- Opioid agonists acting on mu, kappa, and delta receptors generally inhibited motility in both proximal and distal colon.
- Dynorphin, an endogenous kappa agonist, increased distal colon myoelectric activity.
- Naloxone pretreatment blocked all observed opioid-induced effects.
- In vitro, U 50 488 H and DSLET stimulated distal colon motility while inhibiting proximal colon contractions.
Conclusions:
- Opioid agonists exhibit differential effects on proximal and distal colon motility.
- Dynorphin's stimulatory effect on the distal colon appears to be peripherally mediated.
- Inhibition of overall colonic motility by opioid agonists may be centrally mediated.