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Expression pattern and pharmacology of the rat type IV metabotropic glutamate receptor
P Kristensen1, P D Suzdak, C Thomsen
1Department of Pathology and Histochemistry, Novo Nordisk, Måløv, Denmark.
Abstract:
The mRNA for the type IV metabotropic glutamate receptor (mGluR4) is most prominently expressed in cerebellar granule cells, the olfactory system, the lateral septal nucleus, and most thalamic nuclei, but lower amount of the mRNA is found in many different brain regions. Agonist stimulation as studied in transfected cells was found to inhibit forskolin-stimulated cyclic-adenosine-monophosphate formation through a pertussis toxin-sensitive mechanism. Agonist rank order of potencies was: L-2-amino-4-phosphonobutyrate (L-AP4) > glutamate > (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (t-ACPD) > quisqualate > L-homocysteate = ibotenate. The results suggests that the mGluR4 may be responsible for many, but not all, effects of L-AP4.
Insights
The type IV metabotropic glutamate receptor (mGluR4) mRNA is found in various brain regions. Agonist stimulation inhibits cyclic-adenosine-monophosphate formation, suggesting mGluR4 mediates some L-AP4 effects.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- The type IV metabotropic glutamate receptor (mGluR4) mRNA exhibits prominent expression in specific brain areas like the cerebellum and olfactory system.
- Lower levels of mGluR4 mRNA are detected across numerous other brain regions.
Purpose of the Study:
- To investigate the functional role and pharmacological properties of the metabotropic glutamate receptor 4 (mGluR4).
- To determine the signaling pathway affected by mGluR4 activation.
Main Methods:
- Analysis of mGluR4 mRNA distribution in various brain regions.
- Studying agonist stimulation effects on forskolin-induced cyclic-adenosine-monophosphate (cAMP) formation in transfected cells.
- Assessing the pertussis toxin sensitivity of the signaling pathway.
Main Results:
- Agonist stimulation of mGluR4 was observed to inhibit forskolin-stimulated cAMP formation.
- This inhibition was sensitive to pertussis toxin, indicating a G-protein mediated pathway.
- The rank order of agonist potency was determined as L-2-amino-4-phosphonobutyrate (L-AP4) > glutamate > (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (t-ACPD) > quisqualate > L-homocysteate = ibotenate.
Conclusions:
- The findings suggest that mGluR4 plays a significant role in mediating the effects of L-AP4.
- mGluR4 activation inhibits cAMP production via a pertussis toxin-sensitive mechanism.
- While mGluR4 accounts for many L-AP4 effects, it may not be responsible for all of them.