Mechanism underlying the effect of progesterone on the kainate receptor-mediated response

• Main Authors: Yu, Hui-Min, 游惠敏
• Other Authors: Wu Fong-Sen
• Format: Others
• Language: zh-TW
• Published: 1997
• Online Access: http://ndltd.ncl.edu.tw/handle/44103091060737284985

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.