Differential localization of phosphoinositide-linked metabotropic glutamate receptor (mGluR1) and the inositol 1,4,5-trisphosphate receptor in rat brain

Abstract

The type 1 metabotropic glutamate receptor (mGluR1) is through to act via the phosphoinositide (PI) system with the associated formation of inositol 1,4,5-trisphosphate (IP3) and Ca2+ release. Utilizing immunohistochemistry and in situ hybridization, we have localized protein and mRNA, respectively, for the mGluR1 and the IP3 receptor (IP3R). We have also localized glutamate-linked PI turnover by autoradiography with 3H-cytidine. We observe a striking contrast in localizations of mGluR1 and IP3R both for protein and mRNA. For instance, mGluR1 occurs in the apparent absence of IP3R in neurons of the stratum oriens of the CA1 hippocampus, islands of Calleja, anterodorsal nucleus of thalamus, lateral nucleus of hypothalamus, and the granular cell layer and the deep nuclei of cerebellum. mGluR1 actions in these brain regions may primarily be mediated through the protein kinase C limb of the PI system, as they contain moderate amounts of 3H-phorbol ester binding. The subthalamic nucleus, red nucleus, and Darkshevich's nucleus, which possess high levels of mGluR1, are devoid of both IP3R immunoreactivity and 3H-phorbol ester binding. These reciprocal localizations suggest that mGluR1 actions in many brain areas may not primarily involve IP3, reflecting instead influences on protein kinase C or other second messengers.

Modulatory effects of NMDA on phosphoinositide responses evoked by the metabotropic glutamate receptor agonist 1S,3R‐ACPD in neonatal rat cerebral cortex

“…Of these, glutamate receptor agonists have been shown to stimulate phosphoinositide turnover in cells expressing mGluRla/,B and mGluR5 (Abe et al, 1992;Tanabe et al, 1992;Pickering et al, 1993). The mGluRs linked to phosphoinositide turnover exhibit pharmacological differences (Abe et al, 1992;Aramori & Nakanishi, 1992;Tanabe et al, 1992;Pickering et al, 1993), differential susceptibility to pertussis toxin (Abe et al, 1992;Aramori & Nakanishi, 1992;Pickering et al, 1993) and have been shown to be differentially expressed in rat brain (Abe et al, 1992;Martin et al, 1992;Fotuhi et al, 1993).…”

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).…”

“…Significant differences between drug treatments within each region were determined with 95% confidence intervals. Additional comparisons were made by determining the relative glucose utilization in each region as a ratio of the 14 C concentration of the region to the mean 14 C concentration of whole brain uptake for that animal (relative 2-deoxyglucose uptake) (Mitchell and Crossman, 1984;Sharp et al, 1993;Trugman and James, 1993). The ratio of region/whole brain uptake could then be used for comparisons with Student's t tests.…”

On the effect of ATP in long-term depression of the prefrontal cortex

“…The group 1 mGluRs consists of GluR 1 and mGluR 5 subtypes. Both are present in the medial cerebral cortex; mGluR 5 is located in all cortical layers preferentially at the postsynaptic dendritic spines (Romano et al, 1995), whereas mGluR 1 is present in layers 2/3 (Fotuhi et al, 1993). We tested the effect of CPCOOEt (100 µM), a selective antagonist of mGluR 1 , and compared it to MPEP (30 µM) the preferential mGluR 5 antagonist.…”