Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “PICROTOXIN”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 91 records · Page 5Linked to original sources
PubMedDate not supplied

[Effect of picrotoxin on the Cl-activated ATPase microsomal fraction of bream brain (Abramis brama L.)].

It is found that picrotoxine in range concentrations 0.1-10 microM stimulates the basal Mg(2+)-ATPase from microsomal fraction of fish bream (Abramis brama L.), however decreases activating effect of 10(-5) M GABA on the enzyme. The stimulative effect of picrotoxine dependants on duration of preincubation with microsomes. It was established that basal Mg(2+)-ATP-ase activity was activated by anions (Cl- > Br- > I-). The activated effect of anions on the Mg(2+)-ATP-ase is decreased in the presence 1 microM picrotoxine. It was shown that in the dependence on concentration of the Mg(2+)-ATP (0.2 or 1 mM) in the incubation medium the picrotoxine serves as on activator or inhibitor of the enzyme activity. It is supposed that picrotoxine allosterially influences on the enzyme by the receptor-dependent way.

Adenosine Triphosphatases↗
PubMed1977

The development of spontaneous motility in chick embryos interaction of picrotoxin and GABA.

The effect of the systemic administration of picrotoxin (1 mg/kg egg weight) and GABA (103 mg/kg e.w.) on the spontaneous motility of 11- to 21-day check embryos was studied intact eggs. Embryonal motility was recorded by the method of Kovach (1970). The activating effect of picrotoxin on 11- and 13-day embryos was unaffected by the administration of GABA. In 13- and 17-day-old embryos, GABA did not modify the paroxysmal effect of picrotoxin, but when the two substances were administered together, it prolonged the interparoxysmal intervals. The effect of GABA was most pronounced in 19- and 21-day-old embryos, in which it either stopped picrotoxin paroxysms from developing at all, or noticeably altered the length of the paroxysms, the amplitude of the movements and the length of the interparoxysmal intervals. The results show that the sensitivity of central apparatuses of embryonal spontaneous motility to GABA develops later than the early activatory effect of picrotoxin and are evidence of specific antagonism of these two neutrotropic substances.

Aminobutyrates↗
PubMed1990

Electrical activity and feeding correlates of intracranial hypothalamic injection of GABA, muscimol and picrotoxin in the rats.

Assemblies of electrodes and a cannula were stereotaxically implanted in the ventromedial (VMH), lateral (LHA) and paraventricular (PVH) hypothalamic areas in male albino rats. Electrical activity of these regions was recorded electrographically before and following intracranial injection (ICI) of GABA, muscimol and picrotoxin. In another set of animals, food intake and water intake were also measured. The activity of the ventromedial hypothalamus changed from slow to fast after ICI of GABA and picrotoxin and fast to slow after muscimol. The activity of the lateral hypothalamus changed from slow to fast with ICI of muscimol and picrotoxin and from fast to slow with GABA, while that of the paraventricular hypothalamic nucleus changed from slow to fast with ICI GABA and fast to slow with muscimol and picrotoxin. ICI of GABA into VMH and LHA and muscimol in VMH, LHA and PVH caused a decrease in food intake. Water intake was also decreased after ICI of GABA in PVH and muscimol in LHA and PVH. On the opposite picrotoxin increased food intake in VMA and LHA and water intake in PVH. The possible interaction of GABAergic drugs with the areas of the brain controlling feeding and drinking is being discussed.

Action Potentials↗
PubMed1989

Picrotoxin effects on frog ERG at different background illumination but same stimulus contrast.

The effect of blockade of GABAergic synapses by picrotoxin on the b- and d-wave of frog ERG was investigated under scotopic (0.002 lx), mesopic (2 lx) and photopic (200 lx) background illumination (Ib). Diffuse white stimuli with two levels of contrast (0.5 and 2.5) were used with each Ib. The aim was to compare the effects of picrotoxin at different background levels, but same stimulus contrast. We found that picrotoxin markedly increased the amplitude and rate of rise of the leading edge of the b- and d-wave with each Ib. This effect was most pronounced at mesopic Ib, smaller at photopic Ib and least pronounced at scotopic Ib. It was relatively stronger on the d-wave than on the b-wave amplitude under scotopic and mesopic conditions. Under photopic conditions, the difference between the picrotoxin effect on the b- and d-wave was much smaller. The possible neuronal mechanisms of the above described picrotoxin effects are discussed.

Animals↗
PubMed1988

Picrotoxin, a gamma-aminobutyric acid-receptor antagonist, retards craniofacial development in the weaning rat: II. Effect on mandibular condylar cartilage.

The in vivo effects of picrotoxin, a gamma-aminobutyric acid (GABA)-receptor antagonist, were studied in the mandibular condyles of weaning rats. Male rats 21 days old were treated daily with 2 mg/kg of picrotoxin for a period of 3 weeks. This study revealed that chronic administration of the agent caused a reduction in bone formation in various sites in the mandible, along with significant changes in the structure of the condylar cartilage and its ossification front. The length of the chondroblastic zone increased, yet the length of the hypertrophic zone was reduced. The latter phenomenon was manifested by qualitative changes in the overall structure of various cellular zones, in the appearance of the osteoblasts, and in the pattern of cartilage mineralization. The changes in the condylar cartilage cannot be attributed to a direct effect of picrotoxin; in vitro studies indicated no significant change in the incorporation of 3H-thymidine and 35S-sulfate in picrotoxin-treated cultures. These findings indicate that picrotoxin affects the normal growth of the mandible in an intact, growing animal, probably through an indirect route involving neurons in the central nervous system.

Animals↗
PubMedDate not supplied

[Synergism of picrotoxin with the endogenous convulsants kynurenine and quinolinic acid and its antagonism with their antagonists].

In experiments on mice the existence of common mechanisms of action was revealed in picrotoxin and kynurenine and quinolinic acid. Picrotoxin selectively potentiated convulsions induced by kynurenine and quinolinic acid and the antagonists of these endogenous convulsants--picolinic, kynurenic and xanthurenic acids--selectively antagonized picrotoxin convulsions. GABA-ergic preparations, effective in kynurenine convulsions and the anticonvulsants diazepam and phenobarbital, were highly effective against picrotoxin-induced convulsions also. Puphemid and trimethin indicated for treating petit mal epilepsy, proved ineffective. The obtained data suggest the possibility of action of kynurenine and quinolinic acid via picrotoxin-sensitive subunits of the benzodiazepine-GABA-receptor-ionophore complex.

Animals↗
PubMed1994

gamma-Aminobutyric acid type A receptor antagonists picrotoxin and bicuculline alter acetylcholine channel kinetics in cultured embryonic rat skeletal muscle.

The effects of the classical gamma-aminobutyric acid type A receptor antagonists picrotoxin and bicuculline on nicotinic acetylcholine receptors in cultured embryonic rat skeletal muscle were examined with whole-cell and cell-attached single-channel recording methods. Up to 600 microM picrotoxin had little or no effect on the amplitude of the whole-cell current, whereas bicuculline dose-dependently blocked it, with an IC50 value of 101.2 +/- 8.9 microM. Bicuculline reduced the maximum inducible acetylcholine current without changing the Kd value, suggesting that bicuculline uncompetitively blocked the binding of acetylcholine to its receptor. The elementary nicotinic acetylcholine receptor currents recorded in the cell-attached single-channel recording configuration exhibited properties typical of those recorded in embryonic muscle (approximately 36 pS and approximately 6 msec). Picrotoxin dramatically transformed individual channel openings into briefly interrupted bursts, so that the number of openings increased while the mean open time markedly decreased. Bicuculline decreased mean open time to a lesser but statistically significant degree. The dominant component of the closed time histogram in control recordings occurred at 17 msec, whereas that recorded with picrotoxin occurred at 0.5 msec. Bicuculline prolonged the closed time, with a dominant closed time component at 52 msec. Elementary conductance was not altered by either agent. In conclusion, we found that the gamma-aminobutyric acid type A channel antagonists picrotoxin and bicuculline were also blockers of embryonic nicotinic acetylcholine receptor channels in cultured rat muscle.

Animals↗
PubMed1995

Effect of intracerebroventricular and intrahypothalamic administrations of picrotoxin on basal and stimulated gastric acid secretion.

The effects of intracerebroventricular and intrahypothalamic injections of picrotoxin, a GABA antagonist, on gastric acid secretion were studied in perfused stomachs of rats under anesthesia. Injection of picrotoxin into the lateral cerebroventricle inhibited the 2-deoxy-D-glucose-stimulated acid secretion. In experiments of intrahypothalamic injections, picrotoxin produced a significant depression of 2-deoxy-D-glucose-stimulated acid secretion when administered to the ventromedial hypothalamus but not to the lateral hypothalamus. In contrast, picrotoxin produced a definite stimulatory effect on basal acid secretion when injected to the lateral hypothalamus or ventromedial hypothalamus; the stimulatory effect of the injection to the lateral hypothalamus was greater than that of the injection to the ventromedial hypothalamus. These findings indicate that picrotoxin acts centrally, probably hypothalamus, to depress the 2-deoxy-D-glucose-stimulated acid secretion. On the other hand, blockade of GABA activity in the lateral hypothalamus or ventromedial hypothalamus may elicit gastric acid secretion. These results, indicate that central GABAergic mechanism is important in regulating gastric acid secretion in the rat.

Animals↗
PubMed1990

Binding interactions of convulsant and anticonvulsant gamma-butyrolactones and gamma-thiobutyrolactones with the picrotoxin receptor.

Alkyl-substituted gamma-butyrolactones (GBLs) and gamma-thiobutyrolactones (TBLs) are neuroactive chemicals. beta-Substituted compounds are convulsant, whereas alpha-alkyl substituted GBLs and TBLs are anticonvulsant. The structural similarities between beta-alkyl GBLs and the convulsant picrotoxinin suggested that alkyl substituted GBLs and TBLs act at the picrotoxin receptor. To test this hypothesis we examined the interactions of convulsant and anticonvulsant GBLs and TBLs with the picrotoxin, benzodiazepine and gamma-aminobutyric acid (GABA) binding sites of the GABA receptor complex. All of these convulsants and anticonvulsants studied competitively displaced 35S-t-butylbicyclophosphorothionate (35S-TBPS), a ligand that binds to the picrotoxin receptor. This inhibition of 35S-TBPS binding was not blocked by the GABA antagonist bicuculline methobromide. The convulsant GBLs and TBLs also partially inhibited [3H]muscimol binding to the GABA site and [3H]flunitrazepam binding to the benzodiazepine site, but they did so at concentrations substantially greater than those that inhibited 35S-TBPS binding. The anticonvulsant GBLs and TBLs had no effect on either [3H]muscimol or [3H]flunitrazepam binding. In contrast to the GBLs and TBLs, pentobarbital inhibited TBPS binding in a manner that was blocked by bicuculline methobromide, and it enhanced both [3H]flunitrazepam and [3H]muscimol binding. Both ethosuximide and tetramethylsuccinimide, neuroactive compounds structurally similar to GBLs, competitively displaced 35S-TBPS from the picrotoxin receptor and both compounds were weak inhibitors of [3H] muscimol binding. In addition, ethosuximide also partially diminished [3H]flunitrazepam binding. These data demonstrate that the site of action of alkyl-substituted GBLs and TBLs is different from that of GABA, barbiturates and benzodiazepines. We suggest that the GBLs and TBLs act at the picrotoxin receptor.

4-Butyrolactone↗
PubMed1981

Modification of the macaque's vestibulo-ocular reflex by picrotoxin.

The vestibulo-ocular reflex (VOR) in the macaque was tested by a modified Bárány spinning test before and after subcutaneous administration of 1 mg/kg of picrotoxin. The drug caused a decrease in the nystagmus time constant to a value near that of the cupula and a decrease in mystagmus asymmetry. Picrotoxin prevented diazepam from increasing the time constant of vestibular nystagmus. Furthermore, picrotoxin reduced the nystagmus time constant after vermisectomy, a lesion that increases the nystagmus time constant and prevents some VOR modifications. Because picrotoxin and diazepam interact antagonistically in the gamma-aminobutyric acid (GABA) neurotransmitter system, these results show a role of GABA in the neural network that transforms a short cupula time constant into a longer nystagmus time constant.

Animals↗
PubMed1977

Effect of elevated brain GABA concentrations on the actions of bicuculline and picrotoxin in mice.

gamma-Acetylenic GABA and gamma-vinyl GABA, two catalytic irreversible inhibitors of mammalian brain GABA transaminase that produce several-fold increases in brain GABA concentrations were tested for their effects on bicuculline and picrotoxin-induced seizures and mortality in mice. Neither inhibitor influenced the frequency of seizures or death produced by either bicuculline or picrotoxin. Both inhibitors, however, produced a dose-dependent prolongation of the time to onset of seizures and death induced by picrotoxin but by bicuculline. These results suggest differences in the antagonism by bicuculline and picrotoxin of GABA-mediated neural functions.

Aminobutyrates↗
PubMed1977

Effects of peripheral and local administration of picrotoxin on the release of newly synthesized 3H-dopamine in the caudate nucleus of the cat.

The release of 3H-DA was estimated in superfusates of a superfusion cannula introduced into the caudate nucleus of "encéphale isolé" cats. 3H-DA was continuously formed from L-3,5-3H-tyrosine introduced into the superfusion medium. Injected at the periphery, picrotoxin (2.5 mg/kg, i.p.) markedly enhanced the release of 3H-DA, the effect being particularly pronounced 90 min after the drug injection. The effects of the local introduction of picrotoxin into the substantia nigra and into the caudate nucleus on 3H-DA release were also examined to ensure the specificity of the result. Picrotoxin (10(5) M) added into the superfusing medium of a second superfusion cannula introduced in to the substantia nigra enhanced by 2 to 5 times the release of 3H-DA during the drug application. No effect could be seen when the tip of the superfusion cannula was not exactly localized into the substantia nigra. Although less pronounced, a stimulation of 3H-DA release was also seen when picrotoxin(10(6) M) was added directly into the superfusion medium of the cannula introduced into the caudate nucleus. These results suggest that some gabaergic neurons are involved in the control of DA release by acting on dopaminergic cell bodies or dendrites into the substantia nigra. Other gabaergic neurons may directly or indirectly act on dopaminergic terminals within the caudate nucleus.

Animals↗
PubMedDate not supplied

Selective suppression of forward and recurrent "rapid" inhibition by local application of picrotoxin in area CA1 of rat hippocampal slices.

Living slices of rat hippocampus were used to study the possibility of suppressing forward and recurrent "rapid" inhibition in area CA1 by local application of picrotoxin, an antagonist of ionotropic gamma-aminobutyric acid (GABAA) receptors. Application of picrotoxin to the apical dendrites increased the duration of focal potentials recorded in the radial layer (143.0 +/- 7.5%, n = 5; here and subsequently, results are presented as mean +/- error of the mean and n is the number of experiments) but had no effect on the population peak in the pyramidal layer (103.0 +/- 19.6%, n = 5). This is evidence for the existence of suppression of direct, but not of recurrent inhibition. Application of picrotoxin to the cell body layer, on the other hand, significantly increased the population peak (654.5 +/- 245.1%, n = 4) and provoked convulsive activity in neurons, demonstrating suppression of recurrent inhibition. Local application of picrotoxin was further used to study the question of how completely antagonists of glutamate ionotropic receptors sensitive to alpha-amino-3-hydroxy-S-methyl-4-isoxazole propionic acid (AMPA) suppress inhibition in solutions with low magnesium contents. This question is important for interpreting experimental data obtained from measurements of the components of excitatory postsynaptic potentials (EPSP), which depend on activation of ionotropic glutamate receptors sensitive to N-methyl-d-aspartic acid (NMDA). A number of studies have suggested that even at low concentrations, AMPA receptor antagonists suppress forward inhibition to such an extent that it has no significant effect on measurements of the NMDA component of EPSP. Our data do not contradict this suggestion.

Animals↗
PubMed1996

Frontal cortex leads other brain structures in generalised spike-and-wave spindles and seizure spikes induced by picrotoxin.

Generaliszed spike-and-wave (SW) spindles (5-7 Hz) associated with myoclonic jerks precede the occurrence of regular spikes (2-3 Hz) associated with convulsive seizure induced by picrotoxin. SW spindles occur spontaneously in rodent and cat under some experimental conditions and are considered to be models of human generalised epilepsy. These spindles have been proposed as being led by a thalamic pacemaker. To examine this possibility in picrotoxin-induced SW spindles and seizure spikes, we recorded EEG using chronically implant unipolar electrodes during intravenous picrotoxin infusion in freely behaving rat. The 6 EEG signals were digitally sampled at 1000 Hz. Linear correlation, spectral, coherence and phase analyses were undertaken to determine time differences (TDs) between EEG channels and the brain structure leading seizure activity. One frontal cortex led all other structures during SW spindles. TD between SW spindles in the leading frontal cortex (Fr1) and the contralateral Fr1 was 3.6 + / - 0.5 msec. All ipsilateral structures (hippocampus, thalamus, amygdala, caudate nucleus and occipital cortex) were delayed by more than 3 msec from Fr1 (intralaminar thalamic nuclei - by 6.3 + / - 0.9 msec). TDs of SW spindles between subcortical regions were less than 1.5 msec. Similar relationships with slightly smaller TDs were found with spikes during convulsive seizure except TDs between frontal cortices did not significantly differ from zero. We suggest that seizure activity induced by picrotoxin is led by one Fr1 during SW spindles and by both frontal cortices working as one system during convulsive seizure.

Animals↗
PubMed1982

Anion-dependent modulation of [3H]muscimol binding and of GABA-stimulated [3H]flunitrazepam binding by picrotoxin and related CNS convulsants.

Picrotoxin, isopropylbicyclophosphate (IPTBO) and related CNS-convulsants have allosteric effects on the binding of ligands to the GABA/benzodiazepine receptor complex. When binding experiments were performed at 23 degrees C and at 35 degrees C, these drugs inhibited [3H]muscimol binding and muscimol- or GABA-stimulated [3H]flunitrazepam binding, respectively. Both effects required the presence of C1-, Br-, I- but not of F- or SO4(2-). Picrotoxin and IPTBO could only partially inhibit [3H]muscimol binding. In contrast other GABA antagonists and convulsants like bicuculline, 3 alpha-hydroxy-16-imino-5 beta-17-aza-androstan-11-one (R 5135), strychnine and d-tubocurarine interferred completely with [3H]muscimol binding, also in the absence of those ions mentioned above which were essential for the effects of picrotoxin. Our results support the notion that drugs like picrotoxin and IPTBO which interfere with the GABA receptor effector system, may lead to an allosteric perturbation of GABA-recognition sites.

Animals↗
PubMed1985

Inhibition of intrathecally administered picrotoxin- and bicuculline-induced convulsions in mice by pipecolic acid or GABA.

Pipecolic acid (PA) is an alicyclic amino acid and putative neurotransmitter which may modulate GABAergic transmission in the central nervous system. The present study was designed to investigate the anticonvulsant effect of intrathecally (i.t.) injected PA on picrotoxin- and bicuculline-induced convulsions which are thought to be produced by interactions with GABAergic systems. Intrathecal injections of picrotoxin and bicuculline in mice produced convulsions which were characterized by a rapid onset and short duration. Coadministration of GABA with either bicuculline or picrotoxin, but not strychnine, attenuated the severity of the convulsions. Coadministration of PA also protected against bicuculline- and picrotoxin-induced convulsions. Intrathecal injections of PA produced a dose-related increase in the latency to the onset of these convulsions as well as a decrease in their duration, however PA failed to inhibit the duration of strychnine-induced seizures. The D isomer of PA was found to be more effective than the L isomer as an anticonvulsant in this study. When administered in a high dose (500 micrograms i.t.), the D isomer produced flaccid paralysis while injection of high doses (100-500 micrograms i.t.) of the L isomer actually elicited convulsions. These results further support an interaction between PA and GABAergic activity.

Animals↗
PubMed1990

Resolution of central sites involved in picrotoxin-induced vagal activation and vasopressin release.

This investigation tested the hypotheses that picrotoxin, a drug which blocks the inhibitory effect of gamma-aminobutyric acid (GABA), would, in spinal cord-transected rats, (1) suppress the cardiac vagus when localized to the forebrain and stimulate the cardiac vagus by acting in the brainstem and (2) stimulate the release of vasopressin into the systemic circulation through separate forebrain and brainstem GABAergic mechanisms. An intra-arterial infusion technique allowed for delivery of picrotoxin selectively to either forebrain or brainstem areas. Administration of picrotoxin via the vertebral artery decreased sinus rate and increased circulating levels of vasopressin. Infusion of picrotoxin into the internal carotid artery caused increases in sinus rate, blood pressure and plasma vasopressin. These data support the hypothesis that GABAergic mechanisms at different levels of the neuraxis exert opposite effects on cardiac vagal activity, and that GABAergic mechanisms in both the brainstem and forebrain inhibit the release of AVP into the systemic circulation.

Animals↗
PubMed1987

Differential effects of caffeine, picrotoxin, and pentylenetetrazol on hippocampal afterdischarge activity and wet dog shakes.

We identified changes in hippocampal afterdischarge activity that follow administration of subcon vulsant doses (one-half the convulsant dose) of analeptic agents with known pharmacological action. Long-Evans rats (N = 104) with chronic bipolar electrodes implanted in the dorsal hippocampus, were injected i.p. with saline, caffeine (75 mg/kg), picrotoxin (2 mg/kg), or pentylenetatrazol (20 mg/kg) in 1 ml/kg volume 15 min before testing. Body temperature was measured at the beginning of the session to determine if significant change was associated with any of the treatments. Beginning at 10 microA, current (2-s train of 50-Hz biphasic pulses) was applied to hippocampal electrodes and intensity was increased in 10-microA steps until the afterdischarge sequence was elicited. Afterdischarge threshold, wet dog shake frequency, and the duration of the primary afterdischarge, the postprimary depression, and the rebound afterdischarge were measured. Caffeine administration produced a dramatic prolongation of the rebound afterdischarge, without affecting the duration of the primary afterdischarge. All other afterdischarge variables were unchanged by the caffeine treatment. Because caffeine blocks adenosine receptors at physiologic concentrations, adenosine action is implicated in the termination of the second, but not the first, spike train. Picrotoxin and pentylenetetrazol had no influence on the EEG, despite evidence of slight (1 degrees C) hypothermia. A decrease in wet dog shake frequency, however, was associated with picrotoxin administration. As picrotoxin and pentylenetetrazol are known gamma-aminobutyric acid (GABA) antagonists, the results suggest that GABA is involved minimally, if at all, in the hippocampal afterdischarge sequence.

Animals↗