| Summary: | 碩士 === 國立成功大學 === 生理學研究所 === 85 === The neurosteroid progesterone has been proposed as a
postitive modulator of the γ-aminobutyric acidA (GABAA)
receptor and anegative modulator of the glycine receptor.
Surprisingly,progesterone also potentiates N-methyl-D-aspartate
(NMDA),kainate and α-amino-3-hydroxy-5-methyl-4-
isoxazolepropionate(AMPA) responses. In the present study we
extend these findingsto explore the mechanism of action of
progesterone on the kainatereceptor-mediated response. Using
whole-cell recording methodsin primary cultures of chick spinal
cord neurons, cell were voltage-clamped at -70 mV. Drug
solutions were applied to singleneurons by pressure ejection
from 7-barrel pipets. Progesterone(100 uM) rapidly and
reversibly potentiates the response to 30 uMkainate by 28%. The
effect of progesterone on the kainateresponse is dose-dependent
with an EC50 of 35 uM and maximalpotentiation of 30%.
Potentiation of the kainate response byextracellularly applied
progesterone is not significantly affected byinclusion of a
saturating concertration of progesterone in the electrode
buffer, indicating that progesterone does not actintracellularly
to modulate the kainate response. Furthermore,progesterone
enhances the kainate maximal response with little effect on the
kainate EC50. Cyclothiazide is a potent positivemodulator of
the kainate receptor. Our result demonstrate thatprogesterone
and cyclothiazide act through different sites on the kainate
receptor to potentiate the kainate response, and that there
isnegative interaction between these two sites.
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