Summary
The actions of gamma-D-glutamylglycine (DGG) and cis-2,3-piperidine dicarboxylate (PDA) were studied in thin hippocampal sections of the guinea pig by intracellular recording. DGG and PDA suppressed depolarizations induced in CA3 neurons by short pulses of L-aspartate (Asp), D-homocysteat (DH) or L-glutamate (Glu). Asp-and DH-responses were more susceptible to the antagonists than were Glu-responses. The sensitivity difference between Glu-responses and Asp-or DH-responses was not so pronounced that these antagonists could be used to differentiate between Glu-mediated and Asp-mediated synapses. Glu and Asp pulses induced long hyperpolarizing deflections in some neurons. In about half of these neurons, PDA and DGG were without effect on the hyperpolarizing responses. The depolarizing action of gamma-amino butyric acid was unaffected by DGG and PDA. These antagonists blocked excitatory postsynaptic potentials induced by fimbrial stimulation. These results suggest that DGG and PDA are relatively specific antagonists of excitatory amino acids in the hippocampus, and that Glu (or Asp) is the neurotransmitter released from axons of CA3 neurons.
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References
Alger BE, Nicoll RA (1982) Pharmacological evidence for two kinds of GABA receptor on rat hippocampal pyramidal cells studied in vitro. J Physiol (Lond) 328: 125–141
Andersen P, Dingledine R, Gjerstad L, Langmoen IA, Laursen AM (1980) Two different responses of hippocampal pyramidal cells to application of gamma-amino butyric acid. J Physiol (Lond) 305: 279–296
Baudry M, Lynch G (1979) Regulation of glutamate receptors by cations. Nature 282: 748–750
Blackstad TW (1956) Commissural connections of the hippocampal region in the rat, with special reference to their mode of termination. J Comp Neurol 105: 417–537
Collingridge GL, Kehl SJ, McLennan H (1983a) The antagonism of amino acid-induced excitations of rat hippocampal CA1 neurones in vitro. J Physiol (Lond) 334: 19–31
Collingridge GL, Kehl SJ, McLennan H (1983b) Excitatory amino acids in synaptic transmission in the Schaffer collateralcommissural pathway of the rat hippocampus. J Physiol (Lond) 334: 33–46
Constanti A, Connor JD, Galvan M, Nistri A (1980) Intracellularly-recorded effects of glutamate and aspartate on neurones in the guinea-pig olfactory cortex slice. Brain Res 195: 403–420
Crunelli V, Forda S, Collingridge GL, Kelly JS (1982) Intracellular recorded synaptic antagonism in the rat dentate gyrus. Nature 300: 450–452
Cull-Candy SG (1976) Two types of extrajunctional L-glutamate receptors in locust muscle fibers. J Physiol (Lond) 255: 449–464
Davies J, Evans RH, Francis AA, Jones AW, Watkins JC (1981) Antagonism of excitation of spinal neurones by cis-2,3-piperidine dicarboxylate. J Neurochem 36: 1305–1307
Davies J, Watkins JC (1981) Pharmacology of glutamate and aspartate antagonists on cat spinal neurones. In: Di Chiara G, Gessa GL (eds) Glutamate as transmitters. Raven Press, New York, pp 275–284
Davies J, Watkins JC (1983) Role of excitatory amino acid receptors in mono-and polysynaptic excitation in the cat spinal cord. Exp Brain Res 49: 280–290
Djorup A, Jahnsen H, Laursen AM (1981) The dendritic response to GABA in CA1 of the hippocampal slice. Brain Res 219: 196–201
Evans RH, Watkins JC (1981) Pharmacological antagonists of excitatory amino acid action. Life Sci 28: 1303–1308
Gottlieb DI, Cowan WM (1973) Autoradiographic studies of the commissural and ipsilateral association connections of the hippocampus and dentate gyrus of the rat. J Comp Neurol 149: 393–422
Hablitz JJ, Langmoen IA (1982) Excitation of hippocampal pyramidal cells by glutamate in the guinea-pig and rat. J Physiol (Lond) 325: 317–331
Kondo H, Toyoda J (1980) Dual effect of glutamate and aspartate on the on-center bipolar cell in the carp retina. Brain Res 199: 240–243
Krnjevic K, Ropert N (1981) Septo-hippocampal pathway modulates hippocampal activity by a cholinergic mechanism. Can J Physiol Pharmacol 59: 911–914
Lewis PR, Shute CCD, Silver A (1967) Confirmation from choline acetylase analyses of a massive cholinergic innervation to the rat hippocampus. J Physiol (Lond) 191: 215–224
Lynch G, Rose G, Gall C (1978) Anatomical and functional aspects of the septo-hippocampal projections. In: Functions of the septo-hippocampal system, Ciba foundation symposium 58(new series). Elsevier, Amsterdam, pp 5–20
McLennan H, Liu Jin-rog (1982) The actions of six antagonists of excitatory amino acids on neurones of the rat spinal cord. Exp Brain Res 45: 151–156
Nicoll RA, Alger BE (1981) Synaptic excitation may activate a calcium-dependent potassium conductance in hippocampal pyramidal cell. Science 212: 957–959
Oomura Y, Ooyama H, Sawada M (1974) Analysis of hyperpolarizations induced by glutamate and acetylcholine on Onchidium neurons. J Physiol (Lond) 243: 321–341
Sawada S, Takada S, Yamamoto C (1982) Excitatory actions of homocysteic acid on hippocampal neurons. Brain Res 238: 282–285
Sawada S, Takada S, Yamamoto C (1983) Selective activation of synapses near the tip of drug-ejecting microelectrode, and effects of antagonists of excitatory amino acids in the hippocampus. Brain Res 267: 156–160
Schwartzkroin PA, Andersen P (1975) Glutamic acid sensitivity of dendrites in hippocampal slices in vitro. Adv Neurol 12: 45–51
Segal M (1981) The actions of glutamic acid on neurons in the rat hippocampal slice. In: Di Chiara G, Gessa GL (eds) Glutamate as a neurotransmitter. Raven Press, New York, pp 217–225
Storm-Mathisen J (1978) Localization of putative transmitters in the hippocampal formation, with a note on the connections to septum and hypothalamus. In: Functions of the septo-hippocampal system. Ciba foundation symposium 58 (New series). Elsevier, Amsterdam, pp 49–86
Storm-Mathisen J, Leknes AK, Bore AT, Vaaland JL, Edminson P, Haug FM, Ottersen OP (1983) First visualization of glutamate and GABA in neurones by immunocytochemistry. Nature 301: 517–520
Tal N, Goldberg O, Luini A, Teichberg VI (1982) An evaluation of γ-glutamyl dipeptide derivatives as antagonists of amino acid-induced Na+ fluxes in rat striatum slices. J Neurochem 39: 574–576
Voneida TJ, Vardaris RM, Fush SE, Reiheid CT (1981) The origin of the hippocampal commissure in the rat. Anat Rec 201: 91–103
Yamamoto C (1972) Activation of hippocampal neurons by mossy fiber stimulation in thin brain sections in vitro. Exp Brain Res 14: 423–435
Yamamoto C, Sawada S (1982) Sensitivity of hippocampal neurons to glutamic acid and its analogues. Brain Res 235: 358–362
Yamamoto C, Yamashita H, Chujo T (1976) Inhibitory action of glutamic acid on cerebellar interneurones. Nature 262: 786–787
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Sawada, S., Yamamoto, C. Gamma-D-glutamylglycine and cis-2,3-piperidine dicarboxylate as antagonists of excitatory amino acids in the hippocampus. Exp Brain Res 55, 351–358 (1984). https://doi.org/10.1007/BF00237285
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DOI: https://doi.org/10.1007/BF00237285