Glutamate Antagonists in Rat Hippocampus

Segal, Menahem

doi:10.1111/j.1476-5381.1976.tb07710.x

Cited by 88 publications

(17 citation statements)

References 13 publications

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“…Moreover, they suggest that GLU rather than ASP acts as transmitter in this projection. This is in agreement with histochemical, electrophysiologic, and pharmacologic evidence indicating that GLU is the transmitter in the commissural and associational fibers of the CA3 pyramidal cells in the hippocampus (27)(28)(29). Because multiple fluorescent labeling showed that the majority of the hippocampal fibers projecting to the LSC originate in the very same population of CA3 cells (3 1 ), the same transmitter may be expected to be active in these projections.…”

supporting

confidence: 85%

Amino acid neurotransmission between fimbria-fornix fibers and neurons in the lateral septum of the rat: A microiontophoretic study

Joëls¹,

Urban²

1984

Experimental Neurology

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We investigated the nature of the excitatory amino acid and the type of amino acid receptor involved in the projection of fimbria-fomix (fi-fx) fibers on neurons in the lateral septal complex (LSC) of the rat. It appeared that neurons which were strongly orthodromically activated (SOA) by stimulation of fi-fx fibers were excited by glutamate (GLU) and aspartate (ASP) at much lower ejecting currents than neurons which were only weakly orthodromically excited. In addition, GLU was a stronger agent than ASP, particularly in SOA septal cells. Two amino acid antagonists tested, glutamic acid diethylester (GDEE) and 2-amino-S-phosphonovaleric acid (2-APV), selectively antagonized responses to the amino acid agonists quisqualate (QUIS) and N-methyl-D-aspartate (NMDA), respectively. They also depressed GLU-and ASP-induced responses, although in that case the antagonists frequently had to be expelled with currents higher than those needed to block QUIS-and NMDA-evoked excitations. Furthermore, GDEE frequently antagonized GLU-induced responses better than ASPevoked excitations, whereas 2-APV often blocked responses to ASP more effectively than those to GLU. It was observed that GDEE, ejected with currents that blocked responses to QUIS reversibly, decreased the number of synaptic responses induced in SOA cells by fi-fx stimuli. Synaptically induced excitation in these neurons was consistently una&cted by 2-APV, even when the antagonist was expelled with high currents. According to these results, LSC neurons, in particular the SOA neurons, are more Abbreviations: li-fx-fimbria-fomix; LSC-lateral septal complex; SOA, WOA-strongly, weakly orthodromically activated; GLU-glutamate; ASP-aspartate; GDEE-glutamic acid diethylester, 2-APV-2-amino%phosphonovaleric acid; QUIS-quisqualate; NMDA-N-methylDaspartate; KA-kainic acid.

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supporting

confidence: 85%

Amino acid neurotransmission between fimbria-fornix fibers and neurons in the lateral septum of the rat: A microiontophoretic study

Joëls¹,

Urban²

1984

Experimental Neurology

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“…In the hippocampus, where the 5-HT terminals have a nonuniform distribution, the 5-HT receptors differed somewhat from those in platelets. Methysergide, cyproheptadine LSD and BOL 148 blocked the inhibitory responses to 5-HT whereas cinanserin, mianserin and methiothepin did not exhibit this effect (Segal, 1976;Haigler & Aghajanian, 1977).…”

Section: Discussionmentioning

confidence: 99%

“…The shape change in platelet suspensions was determined with a Born Mark 3 aggregometer by measuring the maximal light absorption at 37°C (M in Figure 1) Segal, 1976). The samples were stirred with a Teflon-covered magnetic stirrer at about 900 revolutions per min.…”

Section: Measurement Of Shape Changementioning

confidence: 99%

Shape Change of Blood Platelets—a Model for Cerebral 5‐hydroxytryptamine Receptors?

Gräf

Pletscher

1979

British J Pharmacology

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In blood platelets of rabbits isolated by a stractan gradient and incubated in a protein‐poor medium, tryptamine, 5‐hydroxytryptamine (5‐HT) and derivatives, quipazine and mescaline caused a shape change. This shape change was inhibited by low concentrations of methysergide. The most potent antagonists of the 5‐HT‐induced shape change included ergoline derivatives and neuroleptic drugs, which showed high stereoselectivity. (‐f)‐Lysergic acid diethylamide ((+)‐LSD), psilocine and some N',N′‐dimethylated tryptamines acted as mixed agonist‐antagonists. The compounds found to be agonists or mixed agonist‐antagonists on platelets have previously been shown to act also as 5‐HT agonists in the central nervous system (CNS). With regard to 5‐HT antagonists, the 5‐HT receptors of platelets reacted differently from those described earlier in brain areas with dense 5‐hydroxytryptaminergic innervation, but showed similarities to 5‐HT receptors investigated previously in spinal cord, cerebral cortex and possibly reticular formation. It is concluded that platelets may be considered with caution as models for some, but not for all, 5‐HT receptors in the CNS.

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“…study of GDEE in the frog spinal cord showed no antagonist activity at the three postsynaptic EAA receptors at concentrations up to 5 mm, and some apparently non-specific effects, with the inhibition of synaptic activity (Evans et al, 1979). In the hippocampus, though, a more selective action of GDEE against EAAs over ACh has been observed (Segal, 1976;Spencer et al, 1983).…”

Section: Introductionmentioning

confidence: 98%

l‐Glutamate diethyl ester and deaminated analogues as excitatory amino acid antagonists in rat cerebral cortex

Turner

Meldrum

1991

British J Pharmacology

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1 The effects of L-glutamate diethyl ester (GDEE) HCl, glutarate diethyl ester (GlrDEE) and glutarate dimethyl ester (GlrDME) on depolarizing responses to a-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), kainate (Kain), N-methyl-D-aspartate (NMDA) and quisqualate (Quis), and spontaneous paroxsymal discharges (SPDs) were examined. Experiments were performed on slices of rat cingulate cortex using the in vitro grease gap recording technique in nominally Mg2 +-free Krebs medium. 2 GDEE HCl (3-14mM) caused a concentration-dependent depolarization of the d.c. baseline potential. L-Glutamate (0.1-0.5mM), HCI (15 mM) and sucrose (30mM) also depolarized the baseline. GlrDEE (3-12 mM) and GlrDME (4-26 mM) had no consistent effect on baseline potential. 3 GDEE HCI (10mM) had no effect on depolarizing responses to AMPA, Kain and NMDA, but caused potentiation of those to Quis with a dose-ratio of 0.53 (0.44-0.63) (n = 4). In two other experiments, where the depolarization of the baseline induced by GDEE HCO was large, a depression of Quis response amplitude was observed. 4 GlrDEE (10mM) antagonized depolarizing responses to Kain, and to a lesser extent NMDA, with dose-ratios of 2.14 (1.92-2.38) and 1.61 (1.39-1.87), respectively. This concentration of GIrDEE had no effect on AMPA responses, but potentiated Quis responses, with a dose-ratio of 0.64 (0.58-0.71). 5 GlrDME (10mM) antagonized depolarizing responses to Kain and to Quis, with dose-ratios of 1.66 (1.48-1.85) and 1.22 (1.15-1.29), respectively, and had no effect on responses to NMDA.6 The SPDs were inhibited by GDEE HCI (IC50 6.7 + 0.37mM), GlrDEE (IC50 5.6 + 0.38 mM) and GlrDME (IC50 10.4 + 0.73 mM). 7 In conclusion, there is little evidence that GDEE HCI is an antagonist of the postsynaptic excitatory amino acid receptors in the rat neocortex, and its effects may result from its contamination with Lglutamate and increased osmolarity of the bathing medium at high concentrations. The deaminated analogues of GDEE are very weak Kain antagonists.

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Glutamate Antagonists in Rat Hippocampus

Cited by 88 publications

References 13 publications

Amino acid neurotransmission between fimbria-fornix fibers and neurons in the lateral septum of the rat: A microiontophoretic study

Amino acid neurotransmission between fimbria-fornix fibers and neurons in the lateral septum of the rat: A microiontophoretic study

Shape Change of Blood Platelets—a Model for Cerebral 5‐hydroxytryptamine Receptors?

l‐Glutamate diethyl ester and deaminated analogues as excitatory amino acid antagonists in rat cerebral cortex

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