DIFFERENTIAL LOCALIZATION OF PHOSPHOINOSITIDE-LINKED METABOTROPIC GLUTAMATE RECEPTOR (MGLUR1) AND THE INOSITOL 1,4,5-TRISPHOSPHATE RECEPTORIN RAT-BRAIN

The type 1 metabotropic glutamate receptor (mGluR1) is thought to act via the phosphoinositide (PI) system with the associated formation of inositol 1,4,5-trisphosphate (IP3) and Ca2+ release. Utilizing immunoh istochemistry and in situ hybridization, we have localized protein and mRNA, respectively, for the mGluR1 and the IP3 receptor (IP3R). We ha ve also localized glutamate-linked PI turnover by autoradiography with H-3-cytidine. We observe a striking contrast in localizations of mGlu R1 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 C A1 hippocampus, islands of Calleja, anterodorsal nucleus of thalamus, lateral nucleus of hypothalamus, and the granular cell layer and the d eep nuclei of cerebellum. mGluR1 actions in these brain regions may pr imarily be mediated through the protein kinase C limb of the PI system , as they contain moderate amounts of H-3-phorbol ester binding. The s ubthalamic nucleus, red nucleus, and Darkshevich's nucleus, which poss ess high levels of mGluR1, are devoid of both IP3R immunoreactivity an d H-3-phorbol ester binding. These reciprocal localizations suggest th at mGluR1 actions in many brain areas may not primarily involve IP3, r eflecting instead influences on protein kinase C or other second messe ngers.