Pentylenetetrazole-induced seizures affect binding site densities for GABA, glutamate and adenosine receptors in the rat brain.
Pentylenetetrazole (PTZ) is a convulsant used to model epileptic seizures in rats. In the PTZ-model, altered heat shock protein 27 (HSP-27) expression highlights seizure-affected astrocytes, which play an important role in glutamate and GABA metabolism. This raises the question whether impaired neurotransmitter metabolism leads to an imbalance in neurotransmitter receptor expression. Consequently, we investigated the effects of seizures on the densities of seven different neurotransmitter receptors in rats which were repeatedly treated with PTZ (40 mg/kg) over a period of 14 days. Quantitative in vitro receptor autoradiography was used to measure the regional binding site densities of the glutamate alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate and N-methyl-D-aspartate (NMDA) receptors, the adenosine receptor type 1 (A(1)), which is part of the system controlling glutamate release, and the gamma-aminobutyric acid (GABA) receptors GABA(A) and GABA(B) as well as the GABA(A)-associated benzodiazepine (BZ) binding sites in each rat. Our results demonstrate altered receptor densities in brain regions of PTZ-treated animals, including the HSP-27 expressing foci (i.e. amygdala, piriform and entorhinal cortex, dentate gyrus). A general decrease of kainate receptor densities was observed together with an increase of NMDA binding sites in the hippocampus, the somatosensory, piriform and the entorhinal cortices. Furthermore, A(1) binding sites were decreased in the amygdala and hippocampal CA1 region (CA1), while BZ binding sites were increased in the dentate gyrus and CA1. Our data demonstrate the impact of PTZ induced seizures on the densities of kainate, NMDA, A(1) and BZ binding sites in epileptic brain. These changes are not restricted to regions showing glial impairment. Thus, an altered balance between different excitatory (NMDA) and modulatory receptors (A(1), BZ binding sites, kainate) shows a much wider regional distribution than that of glial HSP-27 expression, indicating that receptor changes are not following the glial stress responses, but may precede the HSP-27 expression.
Institute for Neuroscience and Medicine (INM-2), Research Centre Jülich, D-52425, Jülich, Germany. c.cremer@fz-juelich.de
C M
CM
Cremer
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N
Palomero-Gallagher
H-J
HJ
Bidmon
A
A
Schleicher
E-J
EJ
Speckmann
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K
Zilles
D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism* / Q000503:physiopathology; D003292:Convulsants / Q000494:pharmacology; D004195:Disease Models, Animal; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D055551:HSP27 Heat-Shock Proteins / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009457:Neuroglia / Q000378:metabolism; D010433:Pentylenetetrazole / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000187:drug effects / Q000378:metabolism; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism; D018079:Receptors, GABA / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D018080:Receptors, GABA-B / Q000187:drug effects / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D013312:Stress, Physiological / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D003292:Convulsants; D055551:HSP27 Heat-Shock Proteins; D010433:Pentylenetetrazole; D043682:Receptor, Adenosine A1; D018091:Receptors, AMPA; D018079:Receptors, GABA; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D018047:Receptors, Purinergic P1; C486114:Hspb1 protein, rat