Metabotropic glutamate receptor mRNA expression in the basal ganglia of the rat

Abstract

Metabotropic glutamate receptors (mGluRs) couple the actions of glutamate to intracellular second messenger systems through G-proteins. The mGluRs play an important role in the regulation of basal ganglia function. Ligand binding studies have revealed that the basal ganglia contain at least two pharmacological types of metabotropic binding sites. Agonists of mGluRs can affect both in vitro electrophysiologic responses of striatal neurons and motor behavior in vivo. Recently, cDNAs encoding five mGluRs have been cloned, each with distinct structural and pharmacological properties. In order to elucidate the function of these receptors in the biology of the extrapyramidal motor system, we have used in situ hybridization to examine the regional and cellular expression patterns of mGluR1-mGluR5 in the adult rat basal ganglia. In the striatum, all of these mGluRs were present in widely varying relative densities and cellular patterns. MGluR5 was particularly prominent, and exhibited a heterogeneous cellular distribution, with labeled and unlabeled populations of neurons. MGluR2 was expressed in a small population of large polygonal striatal neurons. The subthalamic nucleus was the only other basal ganglia structure that expressed mGluR2. Distinct cellular distributions of mGluR expression were also observed within the nucleus accumbens, globus pallidus, ventral pallidum, and substantia nigra pars reticulata. MGluR3 was expressed in glia in all basal ganglia structures, but was observed in neurons only in the striatum, substantia nigra pars reticulata, and very weakly in the subthalamic nucleus. Comparison of the restricted mGluR2 and mGluR3 mRNA distributions with that of metabotropic ligand binding sites supports a possible presynaptic location for these receptors in the basal ganglia. MGluR1 was the only mGluR message prominently expressed in the dopaminergic neurons of the substantia nigra pars compacta, suggesting the involvement of this receptor in the regulation of dopamine release from nigrostriatal terminals.

Simultaneous Blockade of Adenosine A2A and Metabotropic Glutamate mGlu5 Receptors Increase their Efficacy in Reversing Parkinsonian Deficits in Rats

“…Adenosine A 2A receptor mRNA is highly expressed in the striatum, nucleus accumbens, olfactory tubercle, and the globus pallidus (Jarvis et al, 1989) where group I mGlu receptors (including subtypes 1 and 5) are also strongly expressed (Testa et al, 1994). In addition, group I mGlu receptors are present in the subthalamic nucleus (STN) and the substantia nigra pars reticulata (SNr) (Tallaksen-Greene et al, 1998;Testa et al, 1994).…”

“…In addition, group I mGlu receptors are present in the subthalamic nucleus (STN) and the substantia nigra pars reticulata (SNr) (Tallaksen-Greene et al, 1998;Testa et al, 1994). In the striatum, adenosine A 2A receptors are predominantly expressed by g-amino butyric acid (GABA)-enkephalin striatopallidal neurons, where they colocalize with DA D 2 receptors (Fink et al, 1992;MartinezMir et al, 1991) and are also present in 25% of cholinergic interneurons (Schiffmann et al, 1991;Fredholm et al, 2001).…”

“…A growing number of studies in animal models of PD suggest that counteracting glutamatergic hyperactivity by pharmacological blockade of glutamate transmission in the basal ganglia represents the most recent challenge in the treatment of Parkinsonian patients (Rouse et al, 2000). Owing to their high level of expression in the basal ganglia structures: striatum, the internal pallidum and substantia nigra pars reticulata (Testa et al, 1994;Tallaksen-Greene et al, 1998), the group I metabotropic glutamate receptors play a major role in the regulation of these nuclei (Rouse et al, 2000). Indeed, recent studies in rats have emphasized the anti-Parkinsonian action of the selective mGluR antagonist of subtype 5 (mGlu 5 receptor) 2-methyl-6-(phenylethylnyl)-pyridine (MPEP) in 6-OHDA-lesioned rats (Spooren et al, 2000;Breysse et al, 2002Breysse et al, , 2003.…”

Metabotropic Glutamate Agonist-Induced Rotation: A Pharmacological, FOS Immunohistochemical, and [14C]-2-Deoxyglucose Autoradiographic Study

“…Group II (mGluRs 2 and 3) and group III (mGluRs 4 -8) receptors inhibit adenylyl cyclase, although with different pharmacological profiles (for review, see Pin and Duvosin, 1995;Roberts, 1995). Ligand-binding studies have shown the striatum to possess a high density of mGluR binding sites (Albin et al, 1992), and several mGluR mRNAs and proteins are expressed by striatal neurons, including members of all three mGluR groups (Abe et al, 1992;Martin et al, 1992;Shigemoto et al, 1992Shigemoto et al, , 1993Fotuhi et al, 1993;Ohishi et al, 1993a,b;Saugstead et al, 1994;Testa et al, 1994;Joly et al, 1995;Romano et al, 1995).…”

Differential expression of glutamate receptors in avian neural pathways for learned vocalization

“…Upon binding glutamate, the receptors directly gate ion channels (ionotropic receptors) and/or change conformation (metabotropic receptors) to transmit electrical signals between neurons and regulate expression of targeted genes via second messengers. Each receptor subunit/subtype has a unique brain expression pattern indicative of different brain subdivisions or cell types having different glutamate receptor functions (Bahn et al, 1994;Conti et al, 1994;Standaert et al, 1994;Testa et al, 1994). Furthermore, some of these subunits/subtypes have different mRNA splice variants contributing further to the diversity of receptor function.…”