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G protein activation by endomorphins in the mouse periaqueductal gray matter

M Narita1, H Mizoguchi, M Narita

  • 1Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisc. 53226, USA.

Journal of Biomedical Science
|May 16, 2000
PubMed

Insights

Newly discovered endomorphins activate G proteins via mu-opioid receptors in the periaqueductal gray matter (PAG). These endogenous peptides act as partial agonists, showing less efficacy than DAMGO in stimulating G protein activity.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Molecular Biology

Background:

  • The midbrain periaqueductal gray matter (PAG) is crucial for coordinating mu-opioid actions.
  • Endomorphins are newly identified endogenous mu-opioid peptides.

Purpose of the Study:

  • To investigate if endomorphins activate G proteins through mu-opioid receptors in the PAG.
  • To characterize the efficacy and receptor specificity of endomorphins in the PAG.

Main Methods:

  • Autoradiographic [(35)S]GTPgammaS binding assay was used to monitor G protein activation.
  • Concentration-dependent binding studies were performed with endomorphin-1, endomorphin-2, and DAMGO.
  • Receptor specificity was assessed using selective mu-, delta-, and kappa-opioid receptor antagonists.

Main Results:

  • Endomorphin-1 and -2 dose-dependently increased [(35)S]GTPgammaS binding in the mouse PAG.
  • Both endomorphins exhibited maximal stimulation of 72-75%, significantly lower than DAMGO (112%).
  • Mu-opioid receptor antagonists blocked endomorphin-induced binding, while delta- and kappa-antagonists had no effect.

Conclusions:

  • Endomorphin-1 and -2 selectively activate mu-opioid receptors in the mouse PAG.
  • These peptides function as partial agonists, with lower intrinsic activity compared to DAMGO.
  • Findings suggest endomorphins are endogenous ligands that modulate PAG function via partial mu-opioid agonism.

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