Non-N-Methyl-D-Aspartate Glutamate Receptors in Glial Cells and Neurons of the Pineal Gland in a Higher Primate

Abstract

A role for glutamate in signalling mechanisms in the mammalian pineal gland is suggested by the high concentration of the transmitter in pinealocytes and the expression of glutamate receptor subunits in the rat gland. A single type of glutamate binding site has been characterized in the rat and bovine pineal gland, preferentially sensitive to the glutamate agonist α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), a potent inhibitor of melatonin synthesis in vitro. In order to investigate the anatomical basis of a putative role of glutamate in the pineal gland of a higher primate, we performed an immuno-histochemical analysis of the cellular localization of AMPA-type glutamate receptor subunits in the pineal gland of the macaque. Staining obtained with an antibody specific to GluRl receptor sub unit showed that this subunit is present in interstitial cells and astrocyte-like cells located in the parenchyma of the distal part of the gland. An antibody specific to GluR4 subunit stained astrocyte-like cells throughout the gland, however mainly in the proximal part, as well as a network of thin and long astrocytic-like processes located exclusively in the distal part of the gland. Staining obtained with an antibody recognizing both GluR2 and GluR3 subunits and the variant GluR4c exhibits a neuropilar-like pattern heterogeneously distributed throughout the gland. The three antibodies stained neuronal-like cells located mainly in the central part of the gland. These findings reveal that in the primate pineal gland, glutamate can act on glial cells via AMPA-gated receptor channels in unusual subunit configurations that likely underly high calcium permeability. Glutamate-induced responses in astrocytes may either regulate glutamatergic transmission by a stimulation of glutamate transport or modulate pinealocyte activity. Based on the existence of distinct glial subpopulations characterized by the differential distribution of AMPA-type receptor subunits, the anatomical division of the pineal gland into proximal and distal parts indicates a functional partition of the gland in higher primates. Intrapineal neuronal-like cells bearing AMPA-type receptors similar to those present in central neurons may be targets of a glutamatergic central neural input or of neighboring pinealocytes.

AMPA glutamate receptors are required for sensory-organ formation and morphogenesis in the basal chordate

“…3 A, B, and G), which suggests that ciGluAs are required for pineal eye-like organ formation and function. Supporting this idea, GluA expression in the pineal body has been reported in macaques and in the developing rat (57,58). Further experiments, for example, with specific marker antibodies, are needed to confirm whether the ascidian ocellus is indeed homologous with the pineal eye.…”

Central Stimulation of Oxytocin Release in the Lactating Rat by N-Methyl-D-Aspartate: Requirement for Coactivation through Non-NMDA Glutamate Receptors or the Glycine Coagonist Site

“…Ionotropic EAA receptors in general admit both cations with efficacies varying between and within subtypes [51,52], and this depolarizing influx should be selectively reduced by specific ion channel inhibitors. Similar to OT release elicited by AMPA alone [8], relatively high doses of these inhibitors were required and OT release could be eliminated only by coapplication of the blockers.…”

Generation of the Melatonin Endocrine Message in Mammals: A Review of the Complex Regulation of Melatonin Synthesis by Norepinephrine, Peptides, and Other Pineal Transmitters

“…The class I mGluR5 receptor is also present in pineal cells and triggers Ca 2ϩ efflux from intracellular stores Pabst and Redecker, 1999). Other ionotropic Glu receptors have also been reported in the pineal glands of several species (Sato et al, 1993;Mick, 1995;Yatsushiro et al, 2000). In the rat pineal gland GluR1 is functionally expressed in pinealocytes and may participate in a Ca 2ϩ -signaling cascade that enhances and expands the Gluergic signal throughout the pineal gland (Yatsushiro et al, 2000).…”