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PubMed2006

Repeated brief epileptic seizures by pentylenetetrazole cause neurodegeneration and promote neurogenesis in discrete brain regions of freely moving adult rats.

Recurrent epileptic seizures are known to provoke various forms of cellular reorganization in the brains of humans and experimental animals. However, little is known about the mechanism of neuronal cell death resulting from epileptic seizures elicited by GABA antagonists. In the present study, we explored the effect on the central nervous systems of freely moving adult rats, of repeated brief epileptic seizures induced by systemic injection of pentylenetetrazole, a GABA-A receptor antagonist. Starting with minor convulsions, repeated epileptic seizures elicited a progressive increase in seizure severity, culminating in the fully kindled state. Histological examination showed that the epileptic seizures caused overt neuronal cell death in the limbic system, including the hippocampus and amygdala, and its adjoining cortex. During the recurrent epileptic seizures, neurogenesis occurred in the subgranular zone of the hippocampus, the subventricular zone of the lateral ventricle, and the amygdala. This type of pentylenetetrazole-induced neurogenesis was seen at an early stage of epileptogenesis in some regions in which massive cell loss was not evident. This suggests that neurogenesis is not a secondary consequence of neuronal cell death, but rather an independent effect of recurrent epileptic seizures.

Animals↗

PubMed2000

Does fucose or piracetam modify the effect of hypoxia preconditioning against pentylenetetrazol-induced seizures?

To clarify the question whether the duration of hypoxia exposure has an influence on the point in time or the strength of hypoxic preconditioning, hypoxia exposure of rats lasting 1 and 8 h was tested regarding the modification of susceptibility to acute pentylenetetrazol-induced seizures. Following the short-lasting (1 h) hypoxia, the maximum level of preconditioning action was observed 7 days after hypoxia, whereas the longer-lasting hypoxia (8 h) produced the maximum level of protection 14 days after hypoxia. We investigated the influence of fucose and piracetam on the effect of hypoxia preconditioning by the application of the substances 20 min before the beginning of hypoxia exposure. Fucose did not modify the result of hypoxia preconditioning. But after the treatment with piracetam, the preconditioning effect was prevented following hypoxia lasting 1 and 8 h. We suggest that the radical scavenger properties of piracetam are responsible for the absence of protection against pentylenetetrazol-evoked seizures.

Animals↗

PubMed2001

Differential effects of pentylenetetrazol-kindling on long-term potentiation of population excitatory postsynaptic potentials and population spikes in the CA1 region of rat hippocampus.

The effects of pentylenetetrazol-kindling on synaptic transmission and the effectiveness of θ pattern primed-bursts (PBs) for the induction of long-term potentiation (LTP) of population excitatory postsynaptic potentials and population spikes were investigated in hippocampal CA1 of pentylenetetrazol-kindled rats. Experiments were carried out in the control and kindled animals at two post-kindling periods, i.e., 48-144 h (early phase) and 30-33 days (long lasting phase). Field potentials (population excitatory postsynaptic potentials, pEPSPs; and population spikes, PSs) were recorded at the stratum radiatum and the stratum pyramidale following stimulation of the stratum fibers, respectively. PBs were delivered to stratum fibers and PB potentiation was assessed. The results showed that 48-144 h after kindling there was no significant difference for pEPSP slope and PS amplitude between two groups. But at 30-33 days after kindling, the pEPSP slope in the stratum radiatum of kindled animals decreased, whereas the amplitude of PSs increased compared to those of controls. Shortly after kindling, control animals had normal LTP of pEPSP slope and PS amplitude in response to PBs, but kindled rats lack LTP of pEPSP slope and PBs induced LTP of PS amplitude in most of kindled animals. In 30-33 days after kindling, PB potentiation was not observed in the stratum radiatum of kindled animals but PBs induced LTP of PS amplitude, which was significantly greater than that of control animals. The effect is compatible with the hypothesis, which postulates kindling-associated functional deficit in hippocampus, especially CA1, as an explanation for the behavioral deficits seen with the kindling model of epilepsy.

Action Potentials↗

PubMed1997

Examination of persistent effects of repeated administration of pentylenetetrazol on rat hippocampal CA1: evidence from in vitro study on hippocampal slices.

The early and long-lasting effects of pentylenetetrazol-kindling on hippocampal CA1 synaptic transmission were investigated. Experiments were carried out in the hippocampal slices from control and kindled rats at two post-kindling periods, i.e. 48-144 h (early phase) and 30-33 days (long-lasting phase). Field potentials, i.e. population excitatory postsynaptic potential (pEPSP) and population spike (PS) were recorded at the stratum pyramidale following stimulation of the stratum radiatum. Kindling-induced changes in synaptic transmission were assessed by stimulus-response functions and paired-pulse responses. The results showed that 48-144 h after kindling, the PS amplitude in the CA1 of kindled slices enhanced, and a second PS appeared compared to control slices. But at 30-33 days after kindling, the pEPSP slope in the CA1 of kindled slices enhanced without any change in the PS compared with those in the control slices. Evaluation of paired-pulse responses showed a significant reduction in paired-pulse inhibition for PS 48-144 h after kindling and a significant increase in paired-pulse inhibition for pEPSP 30-33 days after kindling. Our results suggest that pentylenetetrazol-kindling is accompanied by enhanced excitability and a reduction of paired-pulse inhibition in hippocampal CA1. The increased paired-pulse inhibition one month after kindling, may be interpreted as an adaptive process to cope with subsequent seizures.

Analysis of Variance↗

PubMed1997

Strain differences in pentylenetetrazol-kindling development and subsequent potentiation effects.

Rats from two different strains, i.e. Wistar rats and Lister hooded rats, were investigated for their ability to acquire the kindling syndrome. After having received 13 kindling stimulations (injection of pentylenetetrazol), the animals were tested for subsequent alterations in induction and maintenance of hippocampal long-term potentiation (LTP) and, moreover in glutamate binding. It was found that rats from both strains did not differ in the response to the initial injection of pentylenetetrazol (PTZ) and the amplitude of the population spike. This suggests that some aspects of basic central excitability are equivalent. Wistar rats acquired the kindling syndrome rapidly whereas seizure outcome was poor in Lister rats. As regards hippocampal LTP, the population spike was only dramatically increased in Wistar rats after kindling completion. Glutamate binding was not altered in animals from the Lister strain. The results suggest that changes in glutamate binding and the increase in the population spike are characteristic consequences of kindling.

Animals↗

PubMed1998

Pentylenetetrazole (PTZ)-induced c-fos expression in the hippocampus of kindled rats is suppressed by concomitant treatment with naloxone.

Rats were kindled by repeated injections of pentylenetetrazole (PTZ; 37.5 mg/kg; i.p.) in the presence or absence of the opioid receptor antagonist naloxone. Naloxone (10 mg/kg; i.p.) applied 30 min before each PTZ application had no major effect on the seizure development, although a slight decrease in the seizure expression of fully kindled animals could be observed. In the kindled animals, a pronounced but transient increase in c-fos mRNA level was observed in several brain areas after the injection of PTZ. The magnitude of c-fos induction was related to the seizure stage reached. Detectable c-fos mRNA levels in the cortex were observed in rats showing stage four seizures, whereas the expression of c-fos in the hippocampus required stage five kindled seizures. The induction of c-fos expression in the hippocampus of stage five kindled rats but not in other brain areas was prevented by treatment of naloxone prior to each PTZ application. In contrast, a single injection of naloxone to kindled rats was not sufficient to prevent c-fos mRNA expression in the hippocampus. In addition, a single PTZ application (at the higher dose of 45 mg/kg) to rats that were not kindled also caused c-fos expression in several brain regions, but this was not influenced by naloxone. Assuming that c-fos expression reflects neuronal activity our findings suggest a functional role of endogenous opioid peptides in the development of kindling-induced neuronal excitation in the hippocampus. In addition, the excitation of the hippocampus does not appear to be involved in the seizure activity but may be responsible for the impairment of learning in PTZ-kindled rats which can be prevented by pretreatment with naloxone [A. Becker, G. Grecksch, M. Brosz, Naloxone ameliorates the learning deficit induced by pentylenetetrazole kindling in rats, Eur. J. Neurosci. 6 (1994) 1512-1515].

Amygdala↗

PubMed1998

Effects of GABAB receptor antagonism on the development of pentylenetetrazol-induced kindling in mice.

Pentylenetetrazol (PTZ) administered chronically in rodents induces kindling which is considered to be a model of chronic epilepsy mediated through a specific interaction with the GABA-gated chloride ionophore. PTZ kindling also impairs shuttle-box learning indicating a possible modulation of memory storage [A. Becker, G. Grecksch, H. Mathies. The influence of diazepam on learning processes impaired by pentylenetetrazol kindling. Naunyn-Schmiedeberg's Arch. Pharmacol. 349 (1994) 429-496]. Since GABAB receptor antagonism has been shown to improve cognitive performance in rodents and primates we have examined the effects of 3 antagonists; CGP 36742 (3-amino-propyl-n-butyl-phosphinic acid), CGP 56433 ([3-¿1-(S)-[¿3-(cyclohexylmethyl) hydroxyphosphinyl]-2-(S)-hydroxypropyl]-amino]ethyl]benzoic acid) and CGP 61334 ([3-¿[3[(diethoxymethyl)hydroxyphosphinyl]-propyl-amino¿meth yl]-benzoic acid) on the induction of PTZ kindling in mice at 48 h intervals for 8 weeks. Subsequently the mice were tested in an active avoidance paradigm. At the end of the experiment GABAB receptor autoradiography was performed on brain sections from these animals. Seizure intensity increased progressively in control mice reaching by 8 weeks a mean score which corresponded to clonic seizures. The GABAB antagonists suppressed kindling during the first 4 weeks and after that restored the seizure intensity to the level of control animals. The level of kindling was proportional to the avoidance score. The density of GABAB receptor binding in brain sections from PTZ kindled mice was significantly greater than in controls. This was not altered by pretreatment with the GABAB antagonists except in the cerebellum.

Animals↗

PubMed2003

Synergistic interaction between felbamate and lamotrigine against seizures induced by 4-aminopyridine and pentylenetetrazole in mice.

We compared the effects of adding a nonprotective dose of felbamate to increasing single doses of lamotrigine with those of monotherapy and vice versa in CD1 mice. Anticonvulsant effects were evaluated against seizures induced by both 14 mg/kg of 4-aminopyridine and 110 mg/kg of pentylenetetrazole, and neurotoxic effects were evaluated by the rotarod test. Changes in anticonvulsants, gamma-aminobutyric acid (GABA) and glutamate concentrations in the whole brain were also assessed. Lamotrigine increased the potency ratio of felbamate against 4-aminopyridine (1.80, 95% confidence interval (CI) 1.23-2.65, P<0.05) but not against pentylenetetrazole nor on rotarod, the protective index being increased from 12.0 to 17.1 for 4-aminopyridine, with a reduction in brain felbamate, and with an increase in brain GABA. Felbamate increased the potency ratio of lamotrigine against 4-aminopyridine (4.35, 95% CI 2.05-9.25, P<0.05) but not on rotarod, the protective index being increased from 4.4 to 15.7; there were no changes in brain lamotrigine, and changes in brain GABA and/or glutamate were unrelated to the pharmacodynamic effects. In conclusion, a nonprotective dose of lamotrigine increased the therapeutic index of felbamate and vice versa, and these effects appeared to be pharmacodynamic.

4-Aminopyridine↗

PubMed1998

Effects of anticonvulsive drugs on pentylenetetrazol kindling and long-term potentiation in freely moving rats.

Drugs with anticonvulsive properties and different mechanisms of action were compared for their influence on long-term potentiation and pentylenetetrazol kindling in freely moving animals. Rats were chronically implanted with a stimulation electrode in the angular bundle and a recording electrode in the dentate gyrus. Field potentials in the dentate gyrus were elicited and long-term potentiation was induced by stimulation of the perforant pathway. The clinically used drugs or the potentially anticonvulsive drugs, diphenylhydantoin (50 mg/kg), diazepam (0.5 mg/kg), pentobarbital (10 mg/kg), dizocilpine (MK 801, 0.2 mg/kg) and CGP 43487 (2-amino-4-methyl-5-phosphono-3-pentenoic acid-carboxyethylester, 10 mg/kg), were injected before tetanization. In behavioural experiments pentylenetetrazol kindling was performed with pretreatment with the substances in dosages indicated above (except MK 801, 0.3 mg/kg). Field potentials recorded in the interval between drug administration and tetanization were influenced only by diphenylhydantoin which enhanced the population spike amplitude to 128% of control values. However, the substances showed different effects on long-term potentiation. MK 801, CGP 43487 and pentobarbital depressed potentiation; diazepam was without effect. Diphenylhydantoin had a minor influence on induction but significantly impaired maintenance of long-term potentiation. Furthermore, MK 801, CGP 43487, diazepam and pentobarbital differentially depressed kindling whereas phenytoin only slightly influenced it. The consequences as to hypothetical common cellular mechanisms for kindling development and long-term potentiation are discussed.

Animals↗

PubMed1999

Effects of some AMPA receptor antagonists on the development of tolerance in epilepsy-prone rats and in pentylenetetrazole kindled rats.

The non-selective alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) receptor antagonists, 2,3-benzodiazepine derivatives CFM-1 (3,5-dihydro-7,8-dimethoxy-1-phenyl-4H-2,3-benzodiazepin-4-one) and CFM-2 (1-(4'-aminophenyl)-3,5-dihydro-7,8-dimethoxy-4H-2,3-benzodiazepin -4-one), following intraperitoneal (i.p.) administration, were studied against audiogenic seizures in genetically epilepsy-prone rats (GEPRs) or pentylenetetrazole induced kindling in rats. After acute i.p. administration the ED50 values of CFM-1 against the clonic and tonic phases of the audiogenic seizures 30 min after pretreatment were 40 (16-100) and 13 (8-25) micromol kg(-1), respectively. The animals used for chronic study were treated i.p. daily (at 10 h) for 4 weeks with CFM-1 (20 or 50 micromol kg(-1)). Chronic treatment for 2 weeks with CFM-1 gave ED50 values against clonic and tonic seizures of 39 (22-69) and 16 (8-25) micromol kg(-1), respectively, whereas chronic treatment for 4 weeks gave ED50 values against clonic and tonic seizures of 42 (18-98) and 17 (7-41.3) micromol kg(-1), respectively. The duration of anticonvulsant activity observed between 0.5 and 4 h following administration of CFM-1 was similar for acute and chronic treatment. Two groups of Sprague-Dawley rats received CMF (20 or 50 micromol kg(-1)) 30 min before a subconvulsant dose of pentylentetrazole (25 mg kg(-1) i.p.) which is able to increase seizure severity in control animals (i.e., chemical kindling). Pretreatment with CFM-2 delayed the progression of seizure rank during repeated administration of pentylentetrazole. At the end of the period of repeated pentylentetrazole treatment (6 weeks) the mean seizure score was 0 in vehicle treated controls, 4.3 in animals treated with vehicle + pentylentetrazole, 2.2 in rats treated chronically with CFM-2 (20 micromol kg(-1) i.p.) + pentylentetrazole and 1.0 in rats treated repeatedly with CFM-2 (50 micromol kg(-1) i.p.) + pentylenetetrazole. CFM-2 was also able to antagonize the long-term increase in sensitivity of the convulsant effects of GABA function inhibitors in pentylentetrazole-kindled animals. Thus, the administration of a challenge dose of pentylentetrazole (15 mg kg(-1) i.p.) or picrotoxin (1.5 mg kg(-1) i.p.) 15 or 30 days after the end of the repeated treatment showed that animals treated with CFM-2 were significantly protected against seizures induced by pentylentetrazole or picrotoxin. The data suggest that, following repeated treatment, tolerance to the novel AMPA receptor antagonists does not develop (CFM-1 in genetically epilepsy-prone rats and CFM-2 in the pentylentetrazole kindling model of epilepsy). Thirteen minutes after drug injection on days 1, 14 and 28 of chronic treatment the motor impairment induced by these compounds was studied with a rotarod apparatus. The TD50 values for CFM-1 or CFM-2-induced impairment of locomotor performance were similar following acute and repeated treatment. The data also suggest that some novel 2,3-benzodiazepines may have clinical potential for some types of epilepsy.

Animals↗

PubMed2003

Changes in nucleotide hydrolysis in rat blood serum induced by pentylenetetrazol-kindling.

There is growing pharmacological evidence from several animal models of seizure disorders that adenosine possesses endogenous anticonvulsant activity. Apart from being released from cells, adenosine can be produced by the degradation of adenine nucleotides by ectoenzymes or soluble nucleotidases. These enzymes constitute an important mechanism in synaptic modulation, as they hydrolyze ATP, an excitatory neurotransmitter, to adenosine, a neuroprotective compound. We recently demonstrated an increase in ectoenzyme activity in rat brain synaptosomes after pentylenetetrazol-kindling in rats resistant to kindling, suggesting a role for ectonucleotidases in the seizure control. The present work investigates the effect of seizures induced by pentylenetetrazol kindling on the enzymes that could be playing a role in ATP, ADP and AMP hydrolysis to adenosine in rat blood serum. Animals received injections of PTZ (30 mg/kg, i.p., dissolved in 0.9% saline) once every 48 h, totaling 10 stimulations and the controls animals were injected with saline. The hydrolysis of ATP, ADP and AMP were significantly increased (42, 40, and 45%, respectively), while phosphodiesterase activity was unchanged. These results suggest once more that an increase in the ATP diphosphohydrolase and 5'-nucleotidase activities and, possibly, in adenosine levels, could represent an important compensatory mechanism in the development of chronic epilepsy. Moreover, the fact that this increase can also be measured in serum could mean that these enzymes might be useful as plasma markers of seizures in epilepsy.

5'-Nucleotidase↗

PubMed1987

Intraosseous diazepam suppression of pentylenetetrazol-induced epileptogenic activity in pigs.

Intravenous access for the administration of antiepileptic drugs can be both time-consuming and difficult in an actively seizing infant. We conducted a study to examine the intraosseous route as an alternate means of vascular access for the administration of diazepam in a pentylenetetrazol-seizure model in pigs. Epileptogenic activity was induced with pentylenetetrazol 100 mg/kg in 15 domestic swine that had undergone craniotomies for electrocortical recording. Diazepam (0.1 mg/kg) was administered IV (n = 5) or intraosseously (n = 5); control animals received no drug (n = 5). Epileptogenic activity was suppressed below control levels within one minute in the IV group and within two minutes in the intraosseous group. A two-way analysis of variance did not show a significant difference between the IV and intraosseous routes; however, both were significantly different when compared to the control. There also was no significant difference in plasma diazepam levels between the two groups at one, two, five, ten, 15, and 20 minutes. Our study demonstrated that the intraosseous route is a rapid and effective alternative for diazepam administration.

Animals↗

PubMed2001

Decreased susceptibility to pentylenetetrazol-induced seizures after low-frequency transcranial magnetic stimulation in rats.

We studied the effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) on seizure susceptibility in rats. rTMS of 1000 pulses at 0.5 Hz led to a prolonged latency for seizure development after an intraperitoneal injection of pentylenetetrazol. The rTMS effectively prevented the development of status epilepticus of pentylenetetrazol-induced convulsions. These findings indicate that low-frequency rTMS affects the neural excitability, in the direction of anticonvulsive, and therefore, suggest the possibility of therapeutic use of rTMS in epilepsy.

Animals↗

PubMed2002

Pentylenetetrazol-kindling of seizures selectively decreases [3H]-citalopram binding in the CA-3 area of rat hippocampus.

The present study was aimed at determining the changes in the 5-HT transporter activity, in different brain structures after pentylenetetrazol induced kindling of seizures. We examined [3H]-citalopram binding in the rat brain structures, and the neurodegenerative effects in the hippocampal formation using autoradiographic and immunohistochemical methods. A statistically significant and selective reduction in the binding of [3H]-citalopram was found in the CA3 field of the hippocampus (P=0.009), and a similar tendency, close to the significance level, in the dentate gyrus (P=0.05). This effect was accompanied by a loss of neurons and activation of microglia in the hippocampal formation. The present data suggest the important role for CA3- serotonergic innervation in pentylenetetrazol induced kindling of seizures.

Animals↗

PubMed2004

Effect of single injection of pentylenetetrazole in a subconvulsive dose on Cl- conductance of the GABAA-receptor complex.

Muscimol-stimulated Cl(-)conductance in brain cortex synaptoneurosomes from Wistar rats decreased 15 min after single intraperitoneal injection of pentylenetetrazole in a subconvulsive dose. These changes reflected a decrease in functional activity of the GABA(A)-receptor/Cl(-)ionophore complex. Muscimol-stimulated Cl(-)conductance in synaptoneurosomes returned to normal 48 h after pentylenetetrazole administration.

Animals↗

PubMed2001

Effects of ketoconazole on oestrus cycle and convulsant action of pentylenetetrazol in mice.

The frequency of oestrus cycles in female mice was significantly reduced by the implantation of a pellet of subcutaneous ketoconazole (50 mg every 6 days). The effect was more pronounced after 22 days than after 13 days and it was probably related with the progressive reduction in steroid synthesis induced by the inhibition of key steroidogenic P450 cytochromes by the drug. In addition, the influence of ketoconazole on the incidence of seizures after the administration of intraperitoneal pentylenetetrazol was evaluated in female mice. Pentylenetetrazol produced a higher percentage of seizures during dioestrus than during oestrus. Pretreatment with ketoconazole significantly increased the percentage of animals with induced seizures in oestrus but not in dioestrus as compared to controls, probably through reduced progesterone levels. The reduced seizure threshold confirm the modulatory role exerted by progesterone on central nervous system excitability, and may be relevant in epileptic patients undergoing antifungal therapy.

Animals↗

PubMed2002

The additive effect of opioids and nitric oxide in increasing pentylenetetrazole-induced seizure threshold in cholestatic mice.

BACKGROUND: Accumulation of endogenous opioids and overproduction of nitric oxide has been reported in cholestatic mice. It is well known that endogenous opioids and nitric oxide alter the susceptibility of experimental animals to different models of seizure. METHODS: The alterations in clonic seizure thresholds, induced by pentylenetetrazole from 1 to 6 days after bile duct ligation, were evaluated in mice. Whether the pretreatment of cholestatic mice with different doses of opioid receptor antagonist naltrexone, or nitric oxide inhibitor N(omega)-nitro-L-arginine methyl ester would have changed the clonic seizure threshold was also examined. RESULTS: While in sham-operated mice the clonic seizure threshold was similar to that of the thresholds in unoperated controls, a time-dependent increase in the threshold was observed in cholestatic mice, reaching a peak on day 3 after bile duct ligation and declining partially after the 4th day. Chronic pretreatment with naltrexone (2, 5 and 10 mg/kg, i.p.) reversed the increased threshold in cholestatic mice on day 3 after operation in a dose-dependent manner with the highest doses used restoring the threshold to that of the control animals. A similar reversal of the increased threshold was observed after acute (1, 3 and 10 mg/kg, i.p.) or chronic (10 mg/kg, i.p. for 4 days) pretreatment with N(omega)-nitro-L-arginine methyl ester. Moreover, concurrent administration of doses of N(omega)-nitro-L-arginine methyl ester and naltrexone that each separately induced a partial reversal of increased seizure threshold in cholestasis caused a complete restoring of the threshold to the control level. CONCLUSIONS: Based on these findings, both opioid receptors and nitric oxide may be involved in the dramatic increase in pentylenetetrazole-induced seizure threshold in cholestasis.

Animals↗

PubMed1994

Pentylenetetrazole-induced chemoshock affects protein kinase C and substrate proteins in mouse brain.

Protein kinase C (PKC) activity, western blot analysis of PKC alpha, beta, gamma, epsilon, and zeta by isozyme-specific antibodies, and in vitro phosphorylation of endogenous substrate proteins were studied in the mice brain after pentylenetetrazole-induced chemoshock. The PKC isozymes and endogenous substrates in the crude cytosolic and membrane fractions were partially purified by DE-52 columns eluted with buffer A containing 100 or 200 mM KCl. This method consistently separates cytosolic and membrane proteins and various PKC isoforms. The 100 mM KCl eluates from DE-52 columns contain more PKC alpha and beta in both cytosol and membrane than the 200 mM KCl eluates, whereas PKC gamma, epsilon, and zeta appear in equal amounts in these two eluates. The kinase activity assayed by phosphorylation of exogenous histone was increased in the chemoshocked mice in both the cytosol and membrane of 200 mM KCl eluates. In further analysis by immunoblotting, this increased activity was found to be due to the increase in content of PKC gamma isozyme. As for novel-type epsilon and zeta isozymes, they were not altered in the chemoshocked mice. From autoradiography, the endogenous substrate 17-kDa neurogranin, which was shown below 21 kDa, was mostly eluted by 100 mM KCl from the DE-52 column, whereas 43-kDa neuromodulin, which was also demonstrated in sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis, only appeared in the 200 mM KCl eluates. The in vitro phosphorylation of neuromodulin was found to be increased in the chemoshocked mice. Therefore, the increased phosphorylation of neuromodulin and increased content of the PKC gamma isoform were involved in the pentylenetetrazole-induced chemoshock.

Animals↗