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Related Experiment Videos

Spinally mediated opioid antidiarrheal effects.

P K Lemcke1, J E Shook, T F Burks

  • 1Department of Pharmacology, College of Medicine, University of Arizona Health Sciences Center, Tucson 85724.

European Journal of Pharmacology
|January 25, 1991
PubMed
Summary

Spinal cord opioid receptors play a role in regulating intestinal mucosa function. Selective mu (PL017) and delta (DPDPE) opioid agonists administered intrathecally (i.t.) effectively inhibited prostaglandin E2 (PGE2)-induced diarrhea in mice.

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Area of Science:

  • Neuroscience
  • Gastroenterology
  • Pharmacology

Background:

  • Opioid receptors are known to modulate gastrointestinal functions.
  • The role of spinal opioid receptors in regulating intestinal mucosal secretion, specifically in diarrhea, requires further investigation.

Purpose of the Study:

  • To investigate the role of spinal opioid receptors in the regulation of intestinal mucosal function.
  • To assess the antidiarrheal effects of selective mu, delta, and kappa opioid agonists administered intrathecally (i.t.) in a mouse model of prostaglandin E2 (PGE2)-induced diarrhea.

Main Methods:

  • Selective mu (PL017), delta (DPDPE), and kappa (U50,488H) opioid agonists were administered intrathecally (i.t.) in mice.
  • Diarrhea was induced by intraperitoneal (i.p.) injection of prostaglandin E2 (PGE2).

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  • Antidiarrheal effects were assessed in a dose-related manner, and compared to antinociception and gastrointestinal transit inhibition.
  • Main Results:

    • Intrathecal administration of mu (PL017) and delta (DPDPE) opioid agonists dose-dependently inhibited PGE2-induced diarrhea.
    • Kappa opioid agonist (U50,488H) showed minimal antidiarrheal effects.
    • Spinal opioid administration was less potent than intracerebroventricular (i.c.v.) but more effective than peripheral (s.c.) administration.
    • Antidiarrheal effects were antagonized by naloxone, confirming opioid receptor involvement.

    Conclusions:

    • Opioid chemosensitive sites within the spinal cord can modulate diarrhea induced by PGE2.
    • Selective mu and delta opioid agonists possess antidiarrheal activity when administered intrathecally.
    • The spinal cord represents a potential target for antidiarrheal therapies involving opioid receptor modulation.