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Differential regulation of GABA B receptor subunit expression and function.
S A Sands1, K E McCarson, S J Enna
1Department of Pharmacology, Toxicology and Therapeutics, Kansas University School of Medicine, Kansas City, Kansas 66160-7424, USA.
The Journal of Pharmacology and Experimental Therapeutics
|March 22, 2003
Summary
Altered GABA(B) receptor expression in the spinal cord does not always correlate with function. Chronic agonist use leads to desensitization via nongenomic mechanisms, not changes in subunit levels.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- The GABA(B) receptor is a G protein-coupled receptor crucial for neuronal signaling.
- It functions as a heterodimer of GABA(B1) and GABA(B2) subunits.
Purpose of the Study:
- To investigate the relationship between GABA(B) receptor function and subunit expression in the rat lumbar spinal cord.
- To explore changes following pharmacological and physiological manipulation.
Main Methods:
- Formalin-induced hind paw inflammation model.
- Baclofen administration (GABA(B) receptor agonist).
- Guanosine 5'-O-(3-[(35)S]thiotriphosphate) ([(35)S]GTPgammaS) binding assay to measure receptor function.
- Messenger RNA (mRNA) analysis for subunit levels.
Main Results:
- Formalin inflammation increased GABA(B1) and GABA(B2) protein but did not alter receptor function.
- Chronic baclofen treatment induced tolerance and hyperalgesia without changing GABA(B1) or GABA(B2) mRNA levels.
- Baclofen treatment abolished stimulated [(35)S]GTPgammaS binding, indicating functional desensitization.
Conclusions:
- GABA(B) receptor subunit expression (GABA(B1) and GABA(B2)) does not always correlate with receptor function.
- These subunits may have additional cellular functions.
- GABA(B) receptor desensitization during prolonged agonist exposure primarily involves nongenomic mechanisms.