fg-9041 and gamma-glutamylglycine

After electrical stimulation of the optic layer (OL) of superior colliculus (SC) slices, the postsynaptic potential (PSP) was recorded in the superficial gray layer (SGL) of the SC. The degeneration studies of retinotectal or corticotectal inputs to the SGL of the SC indicated that this PSP evoked in the SGL of the SC slices was retinotectal in origin. Neurotransmission in this pathway may be mediated by glutamate, because the PSP amplitude was reduced and blocked by application of kynurenate or quinoxaline dione (DNQX) to the medium. Furthermore, the concentration of glutamate in the right SGL was significantly reduced by 32% after left optic denervation and by 30% after ablation of the right visual cortex, compared with that in the left SGL. Long-term potentiation (LTP) in the SGL was induced by tetanic stimulation (50 Hz, 20 s) to the OL. The LTP formation was facilitated by the removal of Mg2+ from the medium. The effects of glutamate antagonists D-amino-5-phosphonovalerate (D-APV), gamma-D-glutamylglycine (gamma-DGG), and (+)-5-methyl-10,11-dihydro-5H-dibenzo, a,d-cycloheptene-5,10-imine maleate (MK-801) on the induction of LTP were investigated. D-APV (100 microM) or gamma-DGG (1 mM) masked the expression of LTP by tetanic stimulation, however LTP was induced after removal of the agents. LTP formation was observed without further tetanic stimulation following the removal of D-APV from the medium even 80 min after the tetanic stimulation. LTP once formed was not influenced by application of D-APV.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 2-Amino-5-phosphonovalerate; Animals; Aspartic Acid; Denervation; Dibenzocycloheptenes; Dipeptides; Dizocilpine Maleate; Evoked Potentials; Excitatory Amino Acid Antagonists; gamma-Aminobutyric Acid; Glutamates; Glutamic Acid; In Vitro Techniques; Kynurenic Acid; Magnesium; Mice; Nerve Degeneration; Optic Nerve; Quinoxalines; Receptors, N-Methyl-D-Aspartate; Receptors, Neurotransmitter; Superior Colliculi; Visual Cortex

N-Methyl-D-aspartate, kainate, and quisqualate released endogenous adenosine from superfused slices of rat parietal cortex. N-Methyl-D-aspartate-evoked adenosine release was blocked by D,L-2-amino-5-phosphono-valeric acid and (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801), indicating that it was receptor-mediated, although it did not show the expected potentiation in the absence of Mg2+. In contrast, N-methyl-D-aspartate-evoked release of [3H]noradrenaline from the same slices was markedly potentiated in Mg2(+)-free medium. Therefore, the lack of Mg2+ modulation of N-methyl-D-aspartate-evoked adenosine release was not due to depolarization-induced alleviation of the Mg2+ block in the slices. Kainate-evoked adenosine release was diminished by the non-specific excitatory amino acid antagonist, gamma-D-glutamyl-glycine, and kainate- and quisqualate-evoked adenosine release was diminished by 6,7-dinitroquinoxaline-2,3-dione, indicating that these agonists release adenosine by acting at non-N-methyl-D-aspartate receptors. Tetrodotoxin decreased N-methyl-D-aspartate- and kainate-evoked adenosine release by 40% and 19% respectively, indicating that release was mediated in part by propagated action potentials in the slices. Total release of adenosine by N-methyl-D-aspartate, kainate or quisqualate was not diminished in the absence of Ca2+. A second exposure to kainate following restoration of Ca2+ to slices previously depolarized in the absence of Ca2+ resulted in an amount of adenosine release equal to an initial release by slices in the presence of Ca2+, a result suggesting the presence of separate Ca2(+)-dependent and Ca2(+)-independent pools of adenosine. The present experiments demonstrate that activation of all three major subtypes of excitatory amino acid receptors in the cortex releases adenosine, possibly from separate Ca2(+)-dependent and -independent pools. Adenosine released from the cortex following excitatory amino acid stimulation may, by acting at inhibitory P1 purinoceptors, diminish excitatory neurotransmission and protect against excitotoxicity.

Topics: 2-Amino-5-phosphonovalerate; Action Potentials; Adenosine; Animals; Calcium; Cerebral Cortex; Dipeptides; Dizocilpine Maleate; In Vitro Techniques; Kainic Acid; Kinetics; Magnesium; Male; N-Methylaspartate; Norepinephrine; Quinoxalines; Quisqualic Acid; Rats; Rats, Inbred Strains; Tetrodotoxin

Our previous studies showed that the survival of cerebellar granule cells in culture is promoted by treatment with N-methyl-D-aspartate. Here we report on the influence of another glutamate analogue, kainic acid, which, in contrast to N-methyl-D-aspartate, is believed to stimulate transmitter receptors mediating fast excitatory postsynaptic potentials. The kainate effect was complex: increased survival at low concentrations (the maximum, at 25-50 microM, was about 50% promotion), whereas concentrations exceeding 50 microM resulted first in a loss of the effect, and then at concentrations of 2-5 x 10(-4) M cells became vulnerable to kainate. The trophic influence of kainate is mediated through receptors other than the N-methyl-D-aspartate preferring subtype. In contrast to the effect of N-methyl-D-aspartate, that of kainate did not depend on the medium K+ level and was potently blocked by dinitroquinoxalinedione, which--at the concentration used here--did not counteract the promotion of cell survival evoked by N-methyl-D-aspartate. Quisqualate was a potent inhibitor of the rescue by kainate. Furthermore, blockade of N-methyl-D-aspartate receptors with the selective antagonists MK-801 or aminophosphonovalerate did not inhibit, but rather potentiated the trophic effect of kainate. Possible mechanisms underlying the trophic effect of chronic depolarization or treatment with excitatory amino acids are discussed, and it is proposed that they involve elevated free cytoplasmic calcium activity following increased influx through voltage-sensitive Ca2+ channels (high K+ and kainate) or receptorgated channels (N-methyl-D-aspartate).

Topics: alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Animals; Cell Survival; Cells, Cultured; Cerebellum; Dipeptides; Dizocilpine Maleate; DNA; Electric Stimulation; Glutamine; Ibotenic Acid; Kainic Acid; L-Lactate Dehydrogenase; N-Methylaspartate; Potassium; Quinoxalines; Quisqualic Acid; Rats; Rats, Inbred Strains; Receptors, Amino Acid; Receptors, Cell Surface