- Email: [email protected]
228 Inhibitory effect of topiramate on abnormal glutamic transmission in the hippocampal CA3 pyramidal neuron of spontaneously epileptic rats (SER)
s40
227
Immunohistochemical localization of metabotropic glutamate mGluR7b, in the central nervous system of the adult rat
receptors, mGluR7a and
Departments of Morphological Brain Science, Kyoto University, Kyoto 606-01, Japan’, Novartis Pharma Inc., Nervous System Research, Basel, Switzerland2 Ayae Kinoshita’ , Ryuichi Shigemoto ‘, Hitoshi Ohishi’ , Masahiko Takada’ , Peter J. Flor2, Herman van der Putten2, Noboru Mizuno’ The distribution of L-AP4-sensitive metabotropic glutamate receptors, mGluR7a and its splice variant mGluR7b, was examined immunohistochemically using variant-specific antibodies in adult rat. Immunoreacitivity for mGluR7a was extensively distributed in the brain and spinal cord being most intense in the olfactory bulb, fields of projections from mitral cells of the olfactory bulb, globus pallidus, hippocampus, lateral geniculate nucleus, locus coeruleus, superior colliculus, solitary nucleus and medullary and spinal dorsal horns. On the other hand, mGluR7b immunoreactivity was observed in more restricted areas, such as hippocampus and globus pallidus. It is northworthy that mGluR7a is expressed preferentially in the systems for sensory perception of nociceptive, temperature, olfacatory, visual, and taste sensation: mGluR7 may play a role in regulation of release of synaptic transmitters in various sites including sensory systems.
228
INHIBITORY EFFECT OF TOPIRAMATE ON ABNORMAL GLUTAMIC TRANSMISSION IN THE HIPPOCAMPAL CA3 PYRAMIDAL NEURON OF SPONTANEOUSLY EPILEPTIC RATS (SER) .
Dept. of Neurosurg., Hiroshima Univ. School of Medicine, l-2-3, Kasumi, Minami-ku, Hiroshima 734, Japan’, Dept. of Pharmacol., Hiroshima Univ. School of Medicine, l-2-3, Kasumi, Minami-ku, Hiroshima 734, Japan2, Inst. of Lab. Anim., Faculty of Medicine, Kyoto Univ., Yoshida-konoecho, Sakyo-ku, Kyoto 606-01, Japan3 Ryosuke Hanaya’ , Masashi Sasa2, Kumatoshi Ishihara2, Tadao Serikawa3, Koji Iida’, Tomohide Akiiitsu’ , Kaoru Kurisul Topiramate (TPM), a novel antiepileptic drug inhibits the seizures of spontaneously epileptic rat (SER), that exhibits both tonic convulsion and absence-like seizures. A single electrostimulus delivered to the mossy fiber induce a long-lasting depolarization shift accompanied by repetitive firing in hippocampal CA3 pyramidal neurons of SER. Antiepileptic effects of TPM on this abnormal excitability in SER were examined intracellularly with hippocampal slices. TPM (10pM) reduced the abnormal excitability of CA3 neurons without affecting the first spike. At a higher dose of lOO,uM, TPM suppressed the first spikes without affecting the resting membrane potential, number of firing induced by depolarizing pulse applied on the cell, nor Ca2+ spikes. Glutamate-induced deporalization and abnormal excitability of CA3 neurons were inhibited by TPM. These findings suggest that TPM inhibits abnormal firing of the CA3 pyramidal neurons by mainly suppressing the glutamate transmission.
229
‘Priming’
induced by FPCCG-I, a new agonist for metabotropic
Dept. Pharmacol. Tokyo Metro. Inst. Med. Sci., 3-18-22, Honkomagome, TOMOKO
SAITOH,
MICHIKO
ISHIDA,
HARUHIKO
glutamate
receptors.
Bunkyo-ku, Tokyo 113, Japan.
SHINOZAKI
A 3’,3’-difluoride analogue of 2-(carboxycyclopropyl)glycine (CCG), FPCCG-I, is a novel potent agonist for metabotropic glutamate receptors (mGluRs). Once FPCCG-I (O.l-2pM) had been applied to the spinal cord preparation of newborn rats, DLcY-aminopimelic acid (3-100pM) got an activity to decrease monosynaptic excitation in a dose dependent manner, showing ‘FPCCG-I priming’. Inhibitory actions of DL-o-aminopimelic acid seen after treatment with F2CCG-I were depressed by antagonists for mG1uR.s in a manner pharmacologically quite similar to those of FZCCG-I. Low concentrations of L-glutamate behaved as a nice substrate for DL-a-aminopimelic acid, and when L-glutamate was simultaneously applied with L-FPCCG-I, the priming was almost completely attenuated, showing that L-glutamate was related to the ‘FPCCG-I priming’. FPCCG-I would provide a useful probe for elucidating the mechanism of the ‘priming’.
227
Immunohistochemical localization of metabotropic glutamate mGluR7b, in the central nervous system of the adult rat
receptors, mGluR7a and
Departments of Morphological Brain Science, Kyoto University, Kyoto 606-01, Japan’, Novartis Pharma Inc., Nervous System Research, Basel, Switzerland2 Ayae Kinoshita’ , Ryuichi Shigemoto ‘, Hitoshi Ohishi’ , Masahiko Takada’ , Peter J. Flor2, Herman van der Putten2, Noboru Mizuno’ The distribution of L-AP4-sensitive metabotropic glutamate receptors, mGluR7a and its splice variant mGluR7b, was examined immunohistochemically using variant-specific antibodies in adult rat. Immunoreacitivity for mGluR7a was extensively distributed in the brain and spinal cord being most intense in the olfactory bulb, fields of projections from mitral cells of the olfactory bulb, globus pallidus, hippocampus, lateral geniculate nucleus, locus coeruleus, superior colliculus, solitary nucleus and medullary and spinal dorsal horns. On the other hand, mGluR7b immunoreactivity was observed in more restricted areas, such as hippocampus and globus pallidus. It is northworthy that mGluR7a is expressed preferentially in the systems for sensory perception of nociceptive, temperature, olfacatory, visual, and taste sensation: mGluR7 may play a role in regulation of release of synaptic transmitters in various sites including sensory systems.
228
INHIBITORY EFFECT OF TOPIRAMATE ON ABNORMAL GLUTAMIC TRANSMISSION IN THE HIPPOCAMPAL CA3 PYRAMIDAL NEURON OF SPONTANEOUSLY EPILEPTIC RATS (SER) .
Dept. of Neurosurg., Hiroshima Univ. School of Medicine, l-2-3, Kasumi, Minami-ku, Hiroshima 734, Japan’, Dept. of Pharmacol., Hiroshima Univ. School of Medicine, l-2-3, Kasumi, Minami-ku, Hiroshima 734, Japan2, Inst. of Lab. Anim., Faculty of Medicine, Kyoto Univ., Yoshida-konoecho, Sakyo-ku, Kyoto 606-01, Japan3 Ryosuke Hanaya’ , Masashi Sasa2, Kumatoshi Ishihara2, Tadao Serikawa3, Koji Iida’, Tomohide Akiiitsu’ , Kaoru Kurisul Topiramate (TPM), a novel antiepileptic drug inhibits the seizures of spontaneously epileptic rat (SER), that exhibits both tonic convulsion and absence-like seizures. A single electrostimulus delivered to the mossy fiber induce a long-lasting depolarization shift accompanied by repetitive firing in hippocampal CA3 pyramidal neurons of SER. Antiepileptic effects of TPM on this abnormal excitability in SER were examined intracellularly with hippocampal slices. TPM (10pM) reduced the abnormal excitability of CA3 neurons without affecting the first spike. At a higher dose of lOO,uM, TPM suppressed the first spikes without affecting the resting membrane potential, number of firing induced by depolarizing pulse applied on the cell, nor Ca2+ spikes. Glutamate-induced deporalization and abnormal excitability of CA3 neurons were inhibited by TPM. These findings suggest that TPM inhibits abnormal firing of the CA3 pyramidal neurons by mainly suppressing the glutamate transmission.
229
‘Priming’
induced by FPCCG-I, a new agonist for metabotropic
Dept. Pharmacol. Tokyo Metro. Inst. Med. Sci., 3-18-22, Honkomagome, TOMOKO
SAITOH,
MICHIKO
ISHIDA,
HARUHIKO
glutamate
receptors.
Bunkyo-ku, Tokyo 113, Japan.
SHINOZAKI
A 3’,3’-difluoride analogue of 2-(carboxycyclopropyl)glycine (CCG), FPCCG-I, is a novel potent agonist for metabotropic glutamate receptors (mGluRs). Once FPCCG-I (O.l-2pM) had been applied to the spinal cord preparation of newborn rats, DLcY-aminopimelic acid (3-100pM) got an activity to decrease monosynaptic excitation in a dose dependent manner, showing ‘FPCCG-I priming’. Inhibitory actions of DL-o-aminopimelic acid seen after treatment with F2CCG-I were depressed by antagonists for mG1uR.s in a manner pharmacologically quite similar to those of FZCCG-I. Low concentrations of L-glutamate behaved as a nice substrate for DL-a-aminopimelic acid, and when L-glutamate was simultaneously applied with L-FPCCG-I, the priming was almost completely attenuated, showing that L-glutamate was related to the ‘FPCCG-I priming’. FPCCG-I would provide a useful probe for elucidating the mechanism of the ‘priming’.