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Mu opioid receptor coupling to Gi/o proteins increases during postnatal development in rat brain
Jeffery N Talbot1, H Kevin Happe, L Charles Murrin
1Depatment of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 985800 Nebraska Medical Center, Omaha, NE 68198-5800, USA.
The Journal of Pharmacology and Experimental Therapeutics
|April 30, 2005
Summary
Mu opioid receptor function, measured by G protein coupling, significantly increases in the adult rat brain compared to neonates. This enhanced function is developmentally regulated and doesn't directly correlate with receptor density.
Area of Science:
- Neuroscience
- Pharmacology
- Developmental Biology
Background:
- Mu opioid receptors are key in the central nervous system, particularly in the striatum.
- Their functional maturation during development is not well understood.
- Striosomes within the striatum are rich in mu opioid receptors.
Purpose of the Study:
- To investigate the developmental changes in G protein coupling of mu opioid receptors in the rat brain.
- To determine if mu opioid receptor expression levels correlate with their functional activation during development.
Main Methods:
- Utilized [(3)H][d-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO) autoradiography to quantify mu opioid receptors.
- Assessed mu opioid receptor activation of G(i/o) proteins via DAMGO-stimulated guanosine 5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPgammaS) binding.
- Analyzed receptor expression and G protein coupling in rat brain sections from postnatal day 5 to adulthood.
Main Results:
- Mu opioid receptor expression showed only a slight increase from postnatal day 5 to adulthood.
- Mu opioid receptor-stimulated G protein coupling increased 20-fold during the same developmental period.
- The ratio of G protein activation per receptor increased 19-fold, indicating enhanced receptor function in adults.
Conclusions:
- Mu opioid receptors are functionally more active in adult rats than in neonates.
- The enhanced G protein coupling is a developmentally regulated process.
- Mu opioid receptor density does not necessarily predict its functional activation during development.