Benzodiazepine and barbiturate ligands modulate responses of cultured hippocampal neurones to the GABA(A) receptor partial agonist, 4-PIOL

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Benzodiazepine and barbiturate ligands modulate responses of cultured hippocampal neurones to the GABA(A) receptor partial agonist, 4-PIOL. / Kristiansen, U.; Lambert, J. D.C.

In: Neuropharmacology, Vol. 35, No. 9-10, 1996, p. 1181-1191.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Kristiansen, U & Lambert, JDC 1996, 'Benzodiazepine and barbiturate ligands modulate responses of cultured hippocampal neurones to the GABA(A) receptor partial agonist, 4-PIOL', Neuropharmacology, vol. 35, no. 9-10, pp. 1181-1191. https://doi.org/10.1016/S0028-3908(96)00070-6

APA

Kristiansen, U., & Lambert, J. D. C. (1996). Benzodiazepine and barbiturate ligands modulate responses of cultured hippocampal neurones to the GABA(A) receptor partial agonist, 4-PIOL. Neuropharmacology, 35(9-10), 1181-1191. https://doi.org/10.1016/S0028-3908(96)00070-6

Vancouver

Kristiansen U, Lambert JDC. Benzodiazepine and barbiturate ligands modulate responses of cultured hippocampal neurones to the GABA(A) receptor partial agonist, 4-PIOL. Neuropharmacology. 1996;35(9-10):1181-1191. https://doi.org/10.1016/S0028-3908(96)00070-6

Author

Kristiansen, U. ; Lambert, J. D.C. / Benzodiazepine and barbiturate ligands modulate responses of cultured hippocampal neurones to the GABA(A) receptor partial agonist, 4-PIOL. In: Neuropharmacology. 1996 ; Vol. 35, No. 9-10. pp. 1181-1191.

Bibtex

@article{ffb4b8b7019c4a388ced67fc4745662e,
title = "Benzodiazepine and barbiturate ligands modulate responses of cultured hippocampal neurones to the GABA(A) receptor partial agonist, 4-PIOL",
abstract = "We have previously characterized 5-(4-piperidyl)isoxazol-3-ol (4-PIOL) as a non-desensitizing partial agonist at GABA(A) receptors and show that the responses are mediated by short-duration channel openings consonant with single-ligand gated openings of the Cl- channels. We presently investigated whether responses of cultured rat hippocampal neurones to 4-PIOL are modulated by benzodiazepine (BDZ) and barbiturate receptor ligands. Whole-cell patch-clamp recordings of maximal responses to 1 mM 4-PIOL were comparable in size to responses evoked by 10 μM of the full GABA(A) agonist, isoguvacine. The BDZ receptor inverse agonist, DMCM (1 μM) reduced responses to isoguvacine (to 65.7 ± 11.0%) and 4-PIOL (to 69.3 ± 3.5%) to a similar extent. The BDZ agonist, midazolam (0.1 μM) potentiated responses to both agonists, and resulted in responses with an early peak with later fading. Potentiation of the peak response to 4-PIOL (to 163 ± 14%) was significantly less than for isoguvacine (215 ± 11%). Pentobarbital (50 μM) caused a very marked, but variable, potentiation of the peak response to 4-PIOL (to 484 ± 93%), which was significantly greater than the potentiation of the peak response to isoguvacine (to 304 ± 46%), and induced fading. This suggests that a relatively larger number of the 4-PIOL-induced channel openings can be transformed to longer duration openings by pentobarbital. In conclusion, responses to 4-PIOL and isoguvacine are modulated by BDZ and barbiturate ligands in a qualitatively similar manner, but with a number of quantitative differences which cannot be readily explained by the kinetic model of Macdonald and Twyman (1992). Investigation of these responses at the single-channel level could provide further insight into the operation of the GABA(A) receptor-ionophore complex.",
keywords = "4-PIOL (5-(4-piperidyl)isoxazol-3-ol), DMCM, GABA(A) receptor partial agonist, Hippocampal neurones in culture, Midazolam, Pentobarbital",
author = "U. Kristiansen and Lambert, {J. D.C.}",
year = "1996",
doi = "10.1016/S0028-3908(96)00070-6",
language = "English",
volume = "35",
pages = "1181--1191",
journal = "Neuropharmacology",
issn = "0028-3908",
publisher = "Pergamon Press",
number = "9-10",

}

RIS

TY - JOUR

T1 - Benzodiazepine and barbiturate ligands modulate responses of cultured hippocampal neurones to the GABA(A) receptor partial agonist, 4-PIOL

AU - Kristiansen, U.

AU - Lambert, J. D.C.

PY - 1996

Y1 - 1996

N2 - We have previously characterized 5-(4-piperidyl)isoxazol-3-ol (4-PIOL) as a non-desensitizing partial agonist at GABA(A) receptors and show that the responses are mediated by short-duration channel openings consonant with single-ligand gated openings of the Cl- channels. We presently investigated whether responses of cultured rat hippocampal neurones to 4-PIOL are modulated by benzodiazepine (BDZ) and barbiturate receptor ligands. Whole-cell patch-clamp recordings of maximal responses to 1 mM 4-PIOL were comparable in size to responses evoked by 10 μM of the full GABA(A) agonist, isoguvacine. The BDZ receptor inverse agonist, DMCM (1 μM) reduced responses to isoguvacine (to 65.7 ± 11.0%) and 4-PIOL (to 69.3 ± 3.5%) to a similar extent. The BDZ agonist, midazolam (0.1 μM) potentiated responses to both agonists, and resulted in responses with an early peak with later fading. Potentiation of the peak response to 4-PIOL (to 163 ± 14%) was significantly less than for isoguvacine (215 ± 11%). Pentobarbital (50 μM) caused a very marked, but variable, potentiation of the peak response to 4-PIOL (to 484 ± 93%), which was significantly greater than the potentiation of the peak response to isoguvacine (to 304 ± 46%), and induced fading. This suggests that a relatively larger number of the 4-PIOL-induced channel openings can be transformed to longer duration openings by pentobarbital. In conclusion, responses to 4-PIOL and isoguvacine are modulated by BDZ and barbiturate ligands in a qualitatively similar manner, but with a number of quantitative differences which cannot be readily explained by the kinetic model of Macdonald and Twyman (1992). Investigation of these responses at the single-channel level could provide further insight into the operation of the GABA(A) receptor-ionophore complex.

AB - We have previously characterized 5-(4-piperidyl)isoxazol-3-ol (4-PIOL) as a non-desensitizing partial agonist at GABA(A) receptors and show that the responses are mediated by short-duration channel openings consonant with single-ligand gated openings of the Cl- channels. We presently investigated whether responses of cultured rat hippocampal neurones to 4-PIOL are modulated by benzodiazepine (BDZ) and barbiturate receptor ligands. Whole-cell patch-clamp recordings of maximal responses to 1 mM 4-PIOL were comparable in size to responses evoked by 10 μM of the full GABA(A) agonist, isoguvacine. The BDZ receptor inverse agonist, DMCM (1 μM) reduced responses to isoguvacine (to 65.7 ± 11.0%) and 4-PIOL (to 69.3 ± 3.5%) to a similar extent. The BDZ agonist, midazolam (0.1 μM) potentiated responses to both agonists, and resulted in responses with an early peak with later fading. Potentiation of the peak response to 4-PIOL (to 163 ± 14%) was significantly less than for isoguvacine (215 ± 11%). Pentobarbital (50 μM) caused a very marked, but variable, potentiation of the peak response to 4-PIOL (to 484 ± 93%), which was significantly greater than the potentiation of the peak response to isoguvacine (to 304 ± 46%), and induced fading. This suggests that a relatively larger number of the 4-PIOL-induced channel openings can be transformed to longer duration openings by pentobarbital. In conclusion, responses to 4-PIOL and isoguvacine are modulated by BDZ and barbiturate ligands in a qualitatively similar manner, but with a number of quantitative differences which cannot be readily explained by the kinetic model of Macdonald and Twyman (1992). Investigation of these responses at the single-channel level could provide further insight into the operation of the GABA(A) receptor-ionophore complex.

KW - 4-PIOL (5-(4-piperidyl)isoxazol-3-ol)

KW - DMCM

KW - GABA(A) receptor partial agonist

KW - Hippocampal neurones in culture

KW - Midazolam

KW - Pentobarbital

UR - http://www.scopus.com/inward/record.url?scp=0030470844&partnerID=8YFLogxK

U2 - 10.1016/S0028-3908(96)00070-6

DO - 10.1016/S0028-3908(96)00070-6

M3 - Journal article

C2 - 9014133

AN - SCOPUS:0030470844

VL - 35

SP - 1181

EP - 1191

JO - Neuropharmacology

JF - Neuropharmacology

SN - 0028-3908

IS - 9-10

ER -

ID: 254466613