Signal transduction, pharmacological properties, and expression patterns of two rat metabotropic glutamate receptors, mGluR3 and mGluR4

Abstract

The metabotropic glutamate receptors are coupled to intracellular signal transduction via G-proteins and consist of a family of at least five different subtypes, termed mGluR1-mGluR5. We studied the signal transduction mechanism and pharmacological characteristics of the rat mGluR3 and mGluR4 subtypes in Chinese hamster ovary cells permanently expressing the cloned receptors. Both mGluR3 and mGluR4 inhibit the forskolin-stimulated accumulation of intracellular cAMP formation in response to agonist interaction. Consistent with the high degree of sequence similarity to mGluR2, mGluR3 closely resembles mGluR2 in its agonist selectivity; the potency rank order of agonists is L-glutamate > trans-1-aminocyclopentane-1,3-dicarboxylate > ibotenate > quisqualate. mGluR4 is totally different in its agonist specificity from any other member of the metabotropic receptors. This receptor potently reacts with L-2-amino-4-phosphonobutyrate (L-AP4) in a stereo-selective manner and moderately responds to L-serine-O-phosphate. mGluR4 thus corresponds well to the putative L-AP4 receptor characterized from brain preparations. Blot and in situ hybridization analyses indicated that both mRNAs are widely distributed in the rat brain. mGluR3 mRNA is highly expressed in neuronal cells of the cerebral cortex and the caudate-putamen, and in granule cells of the hippocampal dentate gyrus. The expression pattern of mGluR4 mRNA is more restricted, and this expression is prominent in the cerebellum, olfactory bulb, and thalamus. Furthermore, the mGluR3 mRNA, unlike the other mRNAs for the metabotropic receptors, is highly expressed in glial cells throughout the brain regions.(ABSTRACT TRUNCATED AT 250 WORDS)

The mGluR2/3 Agonist LY379268 Induced Anti-Reinstatement Effects in Rats Exhibiting Addiction-like Behavior

“…The expression pattern of mGluR2 and mGluR3 was in agreement with previous findings (Ohishi et al, 1993;Tanabe et al, 1993), and showed the highest expression levels for both genes in the cortex and dentate gyrus of the hippocampus (Supplementary Figure S10). No significant differences in mGluR2 and mGluR3 expression were found between 0crit and 3crit rats in any investigated forebrain region.…”

The Taste of Monosodium Glutamate: Membrane Receptors in Taste Buds

“…In transfected Chinese hamster ovary cells, activation of mGluR4 is associated with decreases in CAMP via inhibition of a cyclase (Tanabe et al, 1993). Whether mGluR4 signaling in specific neurons and in taste cells is linked via inhibition of a nucleotide cyclase or via activation of a phosphodiesterase would depend on the presence of appropriate G-proteins and the regulatable enzymes required for these alternative pathways.…”

Differential desensitization of μ‐ and δ‐ opioid receptors in selected neural pathways following chronic morphine treatment

“…5-HTlA receptors and the metabotropic glutamate receptors, mGluR4, and mGluR7, are coupled to inhibition of cyclic AMP synthesis (via GI proteins) and are expressed in the rat thalamus (Tanabe et al, 1993;Okamoto et al, 1994;Martin & Humphrey, 1994;Boess & Martin, 1994). Dose-dependent inhibitions of adenylyl cyclase activity were observed in the thalamus with selective agonists of these receptor types (8-OH-DPAT, L-AP4; glutamate), and their inhibitory actions were antagonized by the selective 5-HTlA antagonist, pindobind-5-HTIA (Liau et al, 1991), and by the mGluR antagonist, MCPG (selective to mGluR negatively coupled to adenylyl cyclase activity) (Kemp et al, 1994), respectively.…”