Effect of penicillin on GABA-gated chloride ion influx

Tsuda, Akemi; Ito, Masako; Kishi, Kazuko; Shiraishi, Hideyuki; Tsuda, Hideo; Mori, Chuzo

doi:10.1007/bf00966719

Cited by 19 publications

(17 citation statements)

References 21 publications

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“…Penicillin is a known convulsant that reduces GABA-evoked currents (Macdonald and Barker, 1977; Horne et al, 1992; Katayama et al, 1992; Tsuda et al, 1994; Behrends, 2000; Sugimoto et al, 2002) and blocks spontaneous activity of GABA A receptors (Krishek et al, 1996; Tierney et al, 1996; Lindquist et al, 2004). This negative modulation is thought to be mediated by open-channel block, as single channel studies have reported decreased open duration with increased channel opening frequency and burst length (Neher and Steinbach, 1978; Chow and Mathers, 1986; Twyman et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Context-dependent modulation of αβγ and αβδ GABAA receptors by penicillin: Implications for phasic and tonic inhibition

2009

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SummaryPenicillin, an open-channel blocker of GABA A receptors, was recently reported to inhibit phasic, but not tonic, currents in hippocampal neurons. To distinguish between isoform-specific and contextdependent modulation as possible explanations for this selectivity, the effects of penicillin were evaluated on recombinant GABA A receptors expressed in HEK293T cells. When co-applied with saturating GABA, penicillin decreased peak amplitude, induced rebound, and prolonged deactivation of currents evoked from both synaptic and extrasynaptic receptor isoforms. However, penicillin had isoform-specific effects on the extent of desensitization, reflecting its ability to differentially modulate peak (non-equilibrium) and residual (near-equilibrium) currents. This suggested that the context of activation could determine the apparent sensitivity of a given receptor isoform to penicillin. To test this hypothesis, we explored the ability of penicillin to modulate synaptic and extrasynaptic isoforms that were activated under more physiologically relevant conditions. Interestingly, while currents evoked from synaptic isoforms under phasic conditions (transient activation by a saturating concentration of GABA) were substantially inhibited by penicillin, currents evoked from extrasynaptic isoforms under tonic conditions (prolonged application by a sub-saturating concentration of GABA) were minimally affected. We therefore concluded that the reported inability of penicillin to modulate tonic currents could not simply be attributed to insensitivity of extrasynaptic receptors, but rather, reflected an inability to modulate these receptors in their native context of activation.

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Section: Introductionmentioning

confidence: 99%

Context-dependent modulation of αβγ and αβδ GABAA receptors by penicillin: Implications for phasic and tonic inhibition

2009

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“…The stimulatory effect of BLA on behavior is probably related to limitation of GABAergic inhibition in CNS [6,7]. It is also possible that BLAinduced blockade of GABA subtype receptors on serotoninergic neurons of raphe nuclei increases axonal release of serotonin and, similarly to SSRI, modifies the sensitivity of serotonin receptors.…”

Section: Resultsmentioning

confidence: 94%

“…Apart from bactericidal effect, penicillin suppresses the inhibitory GABAergic neurotransmission and amplifies the effects of stimulatory transmitters in the CNS [7]. Modern BLA also increase excitability of neurons [6].…”

mentioning

confidence: 99%

“…β-Lactam antibiotics (BLA) are structurally related antibacterial agents characterized by a common mechanism of antibacterial effect and including penicillin [3]. Apart from bactericidal effect, penicillin suppresses the inhibitory GABAergic neurotransmission and amplifies the effects of stimulatory transmitters in the CNS [7]. Modern BLA also increase excitability of neurons [6].…”

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confidence: 99%

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Antidepressant activity of β-lactam antibiotics and their effects on the severity of serotonin edema

Волчегорский

Trenina

2006

Bull Exp Biol Med

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Injection of beta-lactam antibiotics (reterpen, ceftazidime, and thienam) to mice in doses equivalent to the mean therapeutic doses for humans led to shortening of the duration of behavioral despair in the hanging by the tail test, modified the resistance to serotonin edema, and intensified the exploratory and orientation activity in the open field test. This sum of effects was detected after 10 injections of retarpen and thienam and after single and five-fold administration of ceftazidime. Antidepressant sertraline also shortened the duration of behavioral despair and reduced serotonin edema. An inverse correlation between the duration of behavioral despair and severity of serotonin edema was detected in control mice. The results suggest that beta-lactam antibiotics are characterized by antidepressant effect related to changes in serotonin sensitivity.

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“…Although antioxidant affect has not been evaluated in the study, ameliorative effect of Crataegus oxyacantha might be associated with its high antioxidant level. Furthermore, Tsuda et al (1994) suggested that penicillin exerts its proconvulsant effect by inhibiting GABA-gated chloride ion influx. Alterations in neurotransmitter systems induced extract should be taken into account for inhibitory/excitatory balance to reduce seizure frequency.…”

Section: Figurementioning

confidence: 99%

Ameliorating effect of hawthorn (<i>Crataegus oxyacantha</i>) and physical exercise on acute penicillin induced seizures in gerbils

Çakir¹,

Orallar²,

Çetinkaya³

et al. 2016

Afr. J. Trad. Compl. Alt. Med.

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Background: The aim of the present study was to assess the effect of Hawthorn (Crataegus oxyacantha) and physical activity. We studied its effect on penicillin induced epilepsy. in gerbils. Materal and Methods: Epilepsy was induced by administration of peniciline G (500 IU, ip). The gerbils were divided randomly in four groups (6 animals per each group) and studied as described below: 1) Control group 2) Exercise group (30 min/each day for 8 weeks) (Eg) 3) Extract group, 50mg/kg/day/animal in 1 ml saline, 3 h prior to exercise (Exe) 4) Exercise+Extract + (Exe+Ex). The severity of epilepsy was observed and recorded. Results: The means of latencies (Mean±SE) were 236±45, 369±36, 386±58 and 433±37 ms in groups of control, Exe, Ex, and Exe+Ex respectively. The mean spike latency significantly (P=0,033 F=3,560) decreased in Exe, Ex and Exe+Ex when compared control. Although spike frequency significantly (P<0.05) diminished in groups of Exe and Ex, no significant decrease was observed in control and Exe+Ex. Similar trend was seen for amplitude values. Spike amplitude values were determined to be significantly (P<0.05) lower than those of control and Exe+Ex. Conclusion: Crataegus oxyacantha extract has shown positive affect to ameliorate on some seizure parameters in this study. However, further more advanced physiologic and neurochemical studies are required to determine the mechanisms involved.

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Effect of penicillin on GABA-gated chloride ion influx

Cited by 19 publications

References 21 publications

Context-dependent modulation of αβγ and αβδ GABAA receptors by penicillin: Implications for phasic and tonic inhibition

Context-dependent modulation of αβγ and αβδ GABAA receptors by penicillin: Implications for phasic and tonic inhibition

Antidepressant activity of β-lactam antibiotics and their effects on the severity of serotonin edema

Ameliorating effect of hawthorn (<i>Crataegus oxyacantha</i>) and physical exercise on acute penicillin induced seizures in gerbils

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