Correlative Changes of Pyridoxal Kinase Pyridoxal‐5′‐phosphate and Glutamate Decarboxylase in Brain, During Drug‐induced Convulsions

Tapia, Ricardo; Mora, Miguel Pérez de la; Massieu, Guillermo H.

doi:10.1111/j.1749-6632.1969.tb54276.x

Cited by 57 publications

(8 citation statements)

References 33 publications

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“…That such drugs inhibit cerebral glutamic acid decarboxylase (GAD) has been repeatedly demonstrated (Killam, 1957;Killam & Bain, 1957;Tapia, de la Mora & Massieu, 1969;Wood & Abrahams, 1971) but because of the wide range of their other metabolic effects, the significance of this inhibition in the causation of the seizures is not clear. Recently some convulsant drugs which are not known to interfere with the coenzymic function of pyridoxal phosphate, have been shown to inhibit GAD.…”

Section: Introductionmentioning

confidence: 99%

Seizures induced by allylglycine, 3‐mercaptopropionic acid and 4‐deoxypyridoxine in mice and photosensitive baboons, and different modes of inhibition of cerebral glutamic acid decarboxylase

Horton

Meldrum

1973

British J Pharmacology

151

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Summary 1. DL-C-Allylglycine, 4-deoxypyridoxine hydrochloride and 3-mercaptopropionic acid have been studied with reference to their convulsant effects in mice and in baboons (Papio papio) with photosensitive epilepsy, and their action on the cerebral enzyme synthesizing y-aminobutyric acid (L-glutamate-1-carboxy-lyase).2. In mice, the EI)0 values for seizures following intraperitoneal injection were allylglycine 1-0 mmol/kg body weight, 4-deoxypyridoxine 141 mmol/kg and 3-mercaptopropionic acid 027 mmol/kg. Latency to seizure onset was longest after allylglycine (44-240 min), intermediate after 4-deoxypyridoxine (9-114 min) and shortest after 3-mercaptopropionic acid (2 5-8 min). 3. In Papio papio intravenous administration of subconvulsant doses of allylglycine (0O87-3-1 mmol/kg), or of 4-deoxypyridoxine (0 21 0-53 mmol/kg) enhanced the occurrence and persistence of myoclonic responses to intermittent photic stimulation, and augmented the associated electroencephalographic abnormalities, without modifying their character or distribution. Higher doses produced brief seizures recurring at regular intervals, between 2-14 h after allylglycine (4-0-4-3 mmol/kg) or 1-4 h after 4-deoxypyridoxine (0-53-0{87 mmol/kg). Electroencephalographically these seizures originated unilaterally in the occipital or posterior parietal cortex. 4. In Papio papio photically-induced epileptic responses were enhanced 5-10 min after the intravenous injection of 3-mercaptopropionic acid (009-028 mmoi/kg). A sequence of brief generalized seizures followed bv complete recovery occurred 4-17 min after the injection of 3-mercaptopropionic acid (0 28-0-38 mmol/kg). Fatal status epilepticus followed the injection of 3-mercaptopropionic acid (0 57-0 75 mmol/kg). E.E.G. records showed generalized cortical involvement at the onset of the seizures. 5. L-Glutamate 1-carboxy-lyase (GAD) activity was determined in whole brain homogenates from mice killed at various intervals after receiving i.p. a convulsant dose of one of the compounds. Inhibition of GAD activity was evident 30-60 min before seizure onset following allylglycine or 4-deoxypyridoxine administration, and was maximal (40-60%) just before or during seizure activity. Addition of pyridoxal phosphate to the brain homogenate relieved inhibition produced by 4-deoxypyridoxine but not that produced by allylglycine. Inhibition of GAD activity in brain homogenates from animals killed 2 or * Present address:

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Section: Introductionmentioning

confidence: 99%

Seizures induced by allylglycine, 3‐mercaptopropionic acid and 4‐deoxypyridoxine in mice and photosensitive baboons, and different modes of inhibition of cerebral glutamic acid decarboxylase

Horton

Meldrum

1973

British J Pharmacology

151

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“…There have been several reports con cerning the decrease of B6 concentration in mammals after treatment with anti-B6 drugs (8)(9)(10)12). After administration of an anti-B6 (for example, SC), PLP levels in the brain decreased, the activity of glutamate decar boxylase (GAD) was inhibited, and the level of r-aminobutyric acid (GABA) in the brain was decreased (12,22).…”

Section: Discussionmentioning

confidence: 99%

“…However, up to now, no complete study of the effect of PLP deficiency on AADC activities using both L DOPA and L-5-HTP as substrates in central and peripheral tissues and serum of mammals has been available. It has been found that a decrease of PLP in the brain also decreases the a-ketoglutarate aminotransferase level (8,9). On the other hand, some studies have been made on mouse brain concerning its content of PLP (10), subcellular distribution of B6-vitamers (11), and effect of pyridoxal (PL) administration on the control of PLP and r-aminobutyric acid (12).…”

mentioning

confidence: 99%

Effect of pyridoxal phosphate deficiency on aromatic L-amino acid decarboxylase activity with L-dopa and L-5-hydroxytryptophan as substrates in rats.

Rahman¹,

Nagatsu²,

Sakurai³

et al. 1982

Jpn.J.Pharmacol

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Abstract-This paper describes the distribution of aromatic L-amino acid decarboxylase (AADC) activities in fourteen tissues (eight peripheral tissues and six brain regions) of semicarbazide (SC)-treated rats, using both L DOPA and L-5-hydroxytryptophan (L-5-HTP) as substrates. The distri bution of pyridoxal phosphate (PLP) was also measured in control and SC-treated rats. SC-treatment decreased the PLP concentration in all tissues (about 50-60% of control). AADC activities towards L-DOPA and L-5-HTP as substrates were also decreased significantly in almost all tissues of SC-treated rats. After the addition of exogenous PLP in vitro, AADC activities were recovered only partially in most tissues, but the recovery patterns were not parallel between L-DOPA and L-5-HTP as substrates. L-DOPA decarboxylase activity was more sensitive to PLP-deficiency than L-5-HTP decarboxylase activity in the same tissues. Serum AADC activities were decreased drastically using both L-DOPA and L-5-HTP as substrates . No serum AADC activity was detected in SC-treated rats using L-DOPA as substrate, but low activity was detected in the same sample using L-5-HTP as the substrate; both activities recovered completely after in vitro addition of 10 W PLP in the incubation mixtures.

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“…Apparently the underlying mechanism is the inhibition of brain GABA aminotransferase [40,41]. Interestingly, at higher doses AOAA can cause seizures [39,42,43]. Because AOAA also can inhibit GAD, changes in GABA levels might account for both anticonvulsant and convulsant activities of the drug.…”

Section: Epileptic Seizures and Plpmentioning

confidence: 99%

Functional Modification of Proteins of the Nervous System by Pyridoxal 5′-Phosphate

Tunnicliff

Ngo

1998

Cell Physiol Biochem

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Correlative Changes of Pyridoxal Kinase Pyridoxal‐5′‐phosphate and Glutamate Decarboxylase in Brain, During Drug‐induced Convulsions

Cited by 57 publications

References 33 publications

Seizures induced by allylglycine, 3‐mercaptopropionic acid and 4‐deoxypyridoxine in mice and photosensitive baboons, and different modes of inhibition of cerebral glutamic acid decarboxylase

Seizures induced by allylglycine, 3‐mercaptopropionic acid and 4‐deoxypyridoxine in mice and photosensitive baboons, and different modes of inhibition of cerebral glutamic acid decarboxylase

Effect of pyridoxal phosphate deficiency on aromatic L-amino acid decarboxylase activity with L-dopa and L-5-hydroxytryptophan as substrates in rats.

Functional Modification of Proteins of the Nervous System by Pyridoxal 5′-Phosphate

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