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Opioid receptor-induced GTPgamma35S binding during mouse development

Joshua F Nitsche1, John E Pintar

  • 1Department of Neuroscience and Cell Biology, UMDNJ-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.

Developmental Biology
|December 20, 2002
PubMed

Insights

Functional activation of mu-opioid receptors (MOR) and delta-opioid receptors (DOR) in developing mice shows distinct temporal and regional patterns. This suggests developmental regulation of opioid receptor signaling pathways.

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Pharmacology

Background:

  • G-protein-coupled receptors (GPCRs) are crucial for numerous physiological functions.
  • Limited understanding exists regarding the developmental activation patterns of GPCRs, particularly opioid receptors.
  • Investigating opioid receptor functional activation during ontogeny is essential for understanding neurodevelopment.

Purpose of the Study:

  • To examine the functional activation of mu-opioid receptors (MOR) and delta-opioid receptors (DOR) during mouse embryonic and fetal development.
  • To map the spatiotemporal emergence of MOR and DOR functional activity in the developing brain.
  • To compare the developmental timing of MOR and DOR functional activation with their gene expression.

Main Methods:

  • Utilized GTPgamma(35)S binding autoradiography on mouse embryo and fetus sections from embryonic day 11.5 (e11.5) to birth.
  • Assessed G-protein coupling in response to MOR-specific agonist DAMGO and DOR-specific agonist DPDPE.
  • Correlated functional activity with previously reported MOR-1 and DOR-1 mRNA expression data.

Main Results:

  • MOR functional activation was first detected at e12.5 in the caudate-putamen (CPU), expanding to other brain regions by e15.5.
  • DOR activity emerged later, first observed at e17.5 in the hypothalamus, pons, and medulla, and at postnatal day 1 (p1) in the CPU at lower levels than MOR.
  • While generally coinciding with MOR-1 and DOR-1 mRNA appearance, delayed functional activation was noted in trigeminal ganglia despite early MOR-1 expression.

Conclusions:

  • Demonstrates distinct temporal and regional differences in the functional activation of MOR and DOR during development.
  • Highlights that the appearance of receptor mRNA does not always directly correlate with functional receptor activity.
  • Suggests that the intricate interactions between opioid receptors, G-proteins, and signaling cofactors are under developmental regulation.

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