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Related Experiment Videos

Cholera toxin effects on body temperature changes induced by morphine

L Basilico1, M Parenti, A Fumagalli

  • 1Institute of Pharmacology, Faculty of Sciences, University of Milan, Italy.

Pharmacology, Biochemistry, and Behavior
|March 1, 1997
PubMed
Summary

Cholera toxin, not its B-subunit, alters morphine

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Area of Science:

  • Neuropharmacology
  • Endocrinology
  • Toxicology

Background:

  • Cholera toxin (CTX) is a potent bacterial exotoxin.
  • Opioids, like morphine, significantly affect thermoregulation.
  • The interaction between CTX and opioid-induced thermic responses is not fully understood.

Purpose of the Study:

  • To investigate the impact of cholera toxin (CTX) and its B-subunit on morphine-induced thermic responses in rats.
  • To explore the underlying molecular mechanisms involving G-protein signaling pathways.

Main Methods:

  • Intracerebroventricular (ICV) administration of CTX or its B-subunit to rats.
  • Subsequent ICV challenge with varying doses of morphine to assess body temperature changes.
  • Analysis of Gs(alpha) and Gi(alpha)/Go(alpha) ADP-ribosylation, basal adenylate cyclase activity, and mu-opioid receptor binding in hypothalamic membranes.

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Main Results:

  • CTX, but not the B-subunit, significantly modified morphine's thermic effects, converting hypothermia to hyperthermia.
  • CTX treatment led to decreased Gs(alpha) immunoreactivity and reduced in vitro ADP-ribosylation of Gs(alpha) in hypothalamic membranes.
  • No significant changes were observed in Gi(alpha)/Go(alpha) ADP-ribosylation, basal adenylate cyclase activity, or mu-opioid receptor binding.

Conclusions:

  • Adaptive events secondary to prolonged Gs(alpha) activation by CTX contribute to altered thermic responses to morphine.
  • These findings highlight a role for Gs(alpha) signaling modulation in the neuropharmacological effects of opioids.