1,721,855 research outputs found
Glycine potentiates the stimulation of inositol phospholipid hydrolysis by excitatory amino acids in primary cultures of cerebellar neurons.
No full textGlycine potentiates stimulation of inositol phospholipid hydrolysis by glutamate and N-methyl-D-aspartate, but not by quisqualate or carbamylcholine, in primary cultures of cerebellar granule cells. This potentiation occurs in the absence of extracellular Mg2+, but is more evident when stimulation of inositol phospholipid hydrolysis by N-methyl-D-aspartate is measured in the presence of 1 mM Mg2+. The action of glycine is not antagonized by strychnine. These results suggest that glycine acts as a positive modulator of signal transduction at a specific class of N-methyl-D-aspartate-sensitive glutamate receptors coupled to inositol phospholipid hydrolysis in cerebellar granule cells
Estradiol benzoate decreases nigral GABAergic activity in male rats.
No full textRepeated doses of estradiol benzoate (10 micrograms/kg, s.c., once a day for 2, 5 or 8 days) to male rats decreased gamma-aminobutyric acid (GABA) content and glutamate decarboxylase (GAD) activity in substantia nigra (SN) but failed to change these parameters in hippocampus, cerebral cortex, cerebellum, lateral septum and olfactory tubercle. In the caudate nucleus, estradiol benzoate decreased GABA concentration but did not modify GAD activity. A decrease in nigral GABA concentration and GAD activity was also observed 24 and 48 but not 3 h after a single injection of estradiol benzoate. These data are consistent with results on GAD activity reported by McGinnis et al. in ovariectomized rats. Kinetic analysis of nigral GAD activity revealed that repeated estradiol benzoate injection reduced the Vmax without affecting the Km of GAD. Estradiol benzoate also reduced the rate of nigral GABA accumulation resulting from local infusion of gabaculine, suggesting that the steroid decreases GABA turnover in male rat SN. Hypophysectomy decreased GABA content and GAD activity in SN and GABA content in striatum. Administration of estradiol benzoate for 8 days to hypophysectomized rats failed to decrease further these parameters. Taken together, these data suggest that estradiol benzoate decreases SN GABAergic activity and that the integrity of the pituitary gland is required for this effect
Metabotropic glutamate receptors and the control of chronic pain
No full textOver the past two decades metabotropic glutamate (mGlu) receptor ligands have been investigated for their potential therapeutic effects in different disorders of the central nervous system (CNS), including anxiety, depression, schizophrenia, and neurodegenerative diseases. In addition, it has been widely demonstrated that mGlu receptors are able to modulate pain transmission both in inflammatory and neuropathic pain models. A large number of preclinical studies combining the use of selective ligands with the knockout strategy have revealed more details about the role of the different mGlu receptor subtypes in the modulation of pain information. This review will address the role of mGlu receptors in pain sensitivity focusing on different strategies to achieve pain control by targeting specific mGlu receptor subtypes. Specifically, pharmacological interventions aimed at inhibiting group I mGlu receptor-mediated signaling and/or potentiating groups II and Ill mGlu receptor signaling together with an epigenetic approach leading to an increased expression of mGlu2 receptors will be discussed
Different coupling of excitatory amino acid receptors with Ca2+ channels in primary cultures of cerebellar granule cells
No full textCerebellar granule cells in primary culture express receptors for excitatory amino acids. The activation of these receptors results in an increased uptake of Ca2+, however, the effects are different depending on the agonists used. Aspartate, NMDA and ibotenate are active only in depolarized conditions, whereas kainate and glutamate activate Ca2+ uptake independently from depolarization. The results indicate the presence of two receptor types: kainate recognition site coupled with voltage-independent Ca2+ channels and NMDA recognition site coupled with voltage-dependent Ca2+ channels. © 1985
LTP and PKM zeta in perirhinal cortex
No full textLong-term potentiation (LTP) is thought to underlie learning and memory processes. Protein Kinase M Zeta, the independently active PKC Zeta isoform, is both necessary and sufficient for the maintenance of the late-phase of LTP in the hippocampus and for the long-term storage of spatial information in behavioural tests (Pastalkova et al., 2006). However, little is known about the mechanisms underlying the maintenance of LTP in perirhinal cortex, a cortical region critical for recognition memory. We demonstrate that a ÒspacedÓ tetra-burst stimulation (four 100-Hz bursts at 5-min interburst interval) in perirhinal cortex is able to induce an LTP lasting longer than 5 hours, which is sensitive to protein synthesis inhibitors. The crucial role of PKM Zeta is confirmed by the reversal of LTP maintenance following the application of the peptide inhibitor ZIP. We are currently studying the role of PKM Zeta in depotentiation and investigating mechanisms involved in modifying the synthesis and/or the activation of this Kinase. Pastalkova E et al. (2006) Storage of spatial information by the maintenance mechanism of LTP. Science 313:1141-4
Magnesium ions inhibit the stimulation of inositol phospholipid hydrolysis by endogenous excitatory amino acids in primary cultures of cerebellar granule cells.
No full textOmission of Mg2+ from the incubation buffer results in a six- to eightfold increase in [3H]inositol-1-phosphate ([3H]Ins-1-P) accumulation in primary cultures of cerebellar granule cells at 7-9 days in vitro. This increase is reversed by low concentrations of 2-amino-5-phosphono-valerate (APV), a result indicating that the absence of Mg2+ facilitates the activation of a specific receptor by the endogenous excitatory amino acids (presumably L-glutamate and L-aspartate) released from the granule cells. The absence of Mg2+ also potentiates the action of exogenously applied N-methyl-D-aspartate (NMDA), L-glutamate, L-aspartate, and kainate. In contrast, the action of quisqualate is virtually unaffected by Mg2+ and is resistant to APV inhibition. Addition of the depolarizing agent veratridine enhances the accumulation of [3H]Ins-1-P also in Mg2+-containing buffer. The action of veratridine is antagonized by APV, a result suggesting that, under depolarized conditions, the NMDA receptor can be activated by the endogenously released excitatory amino acids, despite the presence of Mg2+. Accordingly, in the presence of Mg2+, veratridine potentiates the action of exogenously applied NMDA but does not facilitate the action of quisqualate
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