Effects of Picrotoxin Treatment on GABAA Receptor Supramolecular Complexes in Rat Brain

Yoshihisa Ito, Dong Koo Lim, Toshitaka Nabeshima, Ing K. Ho

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Abstract The effects of acute and chronic administration of a subconvulsive dose of picrotoxin on t‐[35S]butylbieyclophosphorothionate ([35S]TBPS), [3H]muscimol, and [3H]flunitrazepam binding characteristics in various regions and on the convulsant potency of picrotoxin in Sprague‐Dawley rats were examined. Acute administration of a sub‐convulsive dose of picrotoxin (3 mg/kg, i. p.) significantly increased [35S]TBPS and [3H]muscimol binding in cerebellum (CB) with no change in frontal cortex (FC). In rats treated chronically with picrotoxin (3 mg/kg, i.p., daily for 10 days), the Bmax of [35S]TBPS binding site was significantly decreased in the FC., striatum (ST), and CB with no change in KD values. Neither [3H]muscimol binding in the FC and CB nor [3H]fiunitrazepam binding in the FC was affected in these rats. In addition, the potency of pentobarbital to inhibit [35S]TBPS binding in vitro was not altered following acute or chronic treatment of picrotoxin. Chronic administration of picrotoxin did not affect convulsive ED50 or LD50 of picrotoxin; however, it delayed the onset of convulsions and increased the time to death. These results suggest that treatment with picrotoxin at a subconvulsive dose for 10 days causes down‐regulation of [35S]TBPS binding sites and that this down‐regulation might be related, at least in part, to the decreased extent of convulsant potency of picrotoxin. In addition, the results indicate possible interaction between convulsant binding sites and GABAA receptor sites in the CB following picrotoxin treatment.

Original languageEnglish
Pages (from-to)1064-1070
Number of pages7
JournalJournal of Neurochemistry
Volume52
Issue number4
DOIs
Publication statusPublished - 01-01-1989
Externally publishedYes

Fingerprint

Picrotoxin
GABA-A Receptors
Rats
Brain
Frontal Lobe
Convulsants
Muscimol
Cerebellum
Binding Sites
Down-Regulation
Flunitrazepam
Lethal Dose 50
Pentobarbital
Seizures

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Ito, Yoshihisa ; Lim, Dong Koo ; Nabeshima, Toshitaka ; Ho, Ing K. / Effects of Picrotoxin Treatment on GABAA Receptor Supramolecular Complexes in Rat Brain. In: Journal of Neurochemistry. 1989 ; Vol. 52, No. 4. pp. 1064-1070.
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abstract = "Abstract The effects of acute and chronic administration of a subconvulsive dose of picrotoxin on t‐[35S]butylbieyclophosphorothionate ([35S]TBPS), [3H]muscimol, and [3H]flunitrazepam binding characteristics in various regions and on the convulsant potency of picrotoxin in Sprague‐Dawley rats were examined. Acute administration of a sub‐convulsive dose of picrotoxin (3 mg/kg, i. p.) significantly increased [35S]TBPS and [3H]muscimol binding in cerebellum (CB) with no change in frontal cortex (FC). In rats treated chronically with picrotoxin (3 mg/kg, i.p., daily for 10 days), the Bmax of [35S]TBPS binding site was significantly decreased in the FC., striatum (ST), and CB with no change in KD values. Neither [3H]muscimol binding in the FC and CB nor [3H]fiunitrazepam binding in the FC was affected in these rats. In addition, the potency of pentobarbital to inhibit [35S]TBPS binding in vitro was not altered following acute or chronic treatment of picrotoxin. Chronic administration of picrotoxin did not affect convulsive ED50 or LD50 of picrotoxin; however, it delayed the onset of convulsions and increased the time to death. These results suggest that treatment with picrotoxin at a subconvulsive dose for 10 days causes down‐regulation of [35S]TBPS binding sites and that this down‐regulation might be related, at least in part, to the decreased extent of convulsant potency of picrotoxin. In addition, the results indicate possible interaction between convulsant binding sites and GABAA receptor sites in the CB following picrotoxin treatment.",
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Effects of Picrotoxin Treatment on GABAA Receptor Supramolecular Complexes in Rat Brain. / Ito, Yoshihisa; Lim, Dong Koo; Nabeshima, Toshitaka; Ho, Ing K.

In: Journal of Neurochemistry, Vol. 52, No. 4, 01.01.1989, p. 1064-1070.

Research output: Contribution to journalArticle

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T1 - Effects of Picrotoxin Treatment on GABAA Receptor Supramolecular Complexes in Rat Brain

AU - Ito, Yoshihisa

AU - Lim, Dong Koo

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N2 - Abstract The effects of acute and chronic administration of a subconvulsive dose of picrotoxin on t‐[35S]butylbieyclophosphorothionate ([35S]TBPS), [3H]muscimol, and [3H]flunitrazepam binding characteristics in various regions and on the convulsant potency of picrotoxin in Sprague‐Dawley rats were examined. Acute administration of a sub‐convulsive dose of picrotoxin (3 mg/kg, i. p.) significantly increased [35S]TBPS and [3H]muscimol binding in cerebellum (CB) with no change in frontal cortex (FC). In rats treated chronically with picrotoxin (3 mg/kg, i.p., daily for 10 days), the Bmax of [35S]TBPS binding site was significantly decreased in the FC., striatum (ST), and CB with no change in KD values. Neither [3H]muscimol binding in the FC and CB nor [3H]fiunitrazepam binding in the FC was affected in these rats. In addition, the potency of pentobarbital to inhibit [35S]TBPS binding in vitro was not altered following acute or chronic treatment of picrotoxin. Chronic administration of picrotoxin did not affect convulsive ED50 or LD50 of picrotoxin; however, it delayed the onset of convulsions and increased the time to death. These results suggest that treatment with picrotoxin at a subconvulsive dose for 10 days causes down‐regulation of [35S]TBPS binding sites and that this down‐regulation might be related, at least in part, to the decreased extent of convulsant potency of picrotoxin. In addition, the results indicate possible interaction between convulsant binding sites and GABAA receptor sites in the CB following picrotoxin treatment.

AB - Abstract The effects of acute and chronic administration of a subconvulsive dose of picrotoxin on t‐[35S]butylbieyclophosphorothionate ([35S]TBPS), [3H]muscimol, and [3H]flunitrazepam binding characteristics in various regions and on the convulsant potency of picrotoxin in Sprague‐Dawley rats were examined. Acute administration of a sub‐convulsive dose of picrotoxin (3 mg/kg, i. p.) significantly increased [35S]TBPS and [3H]muscimol binding in cerebellum (CB) with no change in frontal cortex (FC). In rats treated chronically with picrotoxin (3 mg/kg, i.p., daily for 10 days), the Bmax of [35S]TBPS binding site was significantly decreased in the FC., striatum (ST), and CB with no change in KD values. Neither [3H]muscimol binding in the FC and CB nor [3H]fiunitrazepam binding in the FC was affected in these rats. In addition, the potency of pentobarbital to inhibit [35S]TBPS binding in vitro was not altered following acute or chronic treatment of picrotoxin. Chronic administration of picrotoxin did not affect convulsive ED50 or LD50 of picrotoxin; however, it delayed the onset of convulsions and increased the time to death. These results suggest that treatment with picrotoxin at a subconvulsive dose for 10 days causes down‐regulation of [35S]TBPS binding sites and that this down‐regulation might be related, at least in part, to the decreased extent of convulsant potency of picrotoxin. In addition, the results indicate possible interaction between convulsant binding sites and GABAA receptor sites in the CB following picrotoxin treatment.

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