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- 검색키워드
- 주제어 : Excitatory postsynaptic currents (검색결과 4 건)
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Daisuke Uta,Tsuyoshi Hattori,Megumu Yoshimura 대한배뇨장애요실금학회 2018 International Neurourology Journal Vol.22 No.4
Purpose: Naftopidil ((±)-1-[4-(2-methoxyphenyl) piperazinyl]-3-(1-naphthyloxy) propan-2-ol) is prescribed in several Asian countries for lower urinary tract symptoms suggestive of benign prostatic hyperplasia. Previous animal experiments showed that intrathecal injection of naftopidil abolished rhythmic bladder contraction in vivo. Naftopidil facilitated spontaneous inhibitory postsynaptic currents in substantia gelatinosa (SG) neurons in spinal cord slices. These results suggest that naftopidil may suppress the micturition reflex at the spinal cord level. However, the effect of naftopidil on evoked excitatory postsynaptic currents (EPSCs) in SG neurons remains to be elucidated. Methods: Male Sprague-Dawley rats at 6 to 8 weeks old were used. Whole-cell patch-clamp recordings were made using SG neurons in spinal cord slices isolated from adult rats. Evoked EPSCs were analyzed in Aδ or C fibers. Naftopidil or prazosin, an α1-adrenoceptor blocker, was perfused at 100 μM or 10 μM, respectively. Results: Bath-applied 100 μM naftopidil significantly decreased the peak amplitudes of Aδ and C fiber-evoked EPSCs to 72.0%±7.1% (n=15) and 70.0%±5.5% (n=20), respectively, in a reversible and reproducible manner. Bath application of 10μM prazosin did not inhibit Aδ or C fiber-evoked EPSCs. Conclusions: The present study suggests that a high concentration of naftopidil reduces the amplitude of evoked EPSCs via a mechanism that apparently does not involve α1-adrenoceptors. Inhibition of evoked EPSCs may also contribute to suppression of the micturition reflex, together with nociceptive stimulation.
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Daisuke Uta,Tsuyoshi Hattori,Megumu Yoshimura 대한배뇨장애요실금학회 2019 International Neurourology Journal Vol.23 No.1
Purpose: The aim of this study was to characterize the responsiveness of miniature excitatory postsynaptic currents (mEPSCs) to α1-adrenoceptor blockers in substantia gelatinosa (SG) neurons from the spinal cord to develop an explanation for the efficacy of α1-adrenoceptor blockers in micturition dysfunction. Methods: Male adult Sprague-Dawley rats were used. Blind whole-cell patch-clamp recordings were performed using SG neurons in spinal cord slices. Naftopidil (100μM), tamsulosin (100μM), or silodosin (30μM), α1-adrenoceptor blockers, was perfused. The frequency of mEPSCs was recorded in an SG neuron to which the 3 blockers were applied sequentially with wash-out periods. Individual frequencies in a pair before naftopidil and tamsulosin perfusion were plotted as baseline, and the correlation between them was confirmed by Spearman correlation coefficient; linear regression was then performed. The same procedure was performed before naftopidil and silodosin perfusion. Frequencies of pairs after naftopidil and tamsulosin perfusion and after naftopidil and silodosin perfusion were similarly analyzed. The ratios of the frequencies after treatment to before were then calculated. Results: After the treatments, Spearman ρ and the slope were decreased to 0.682 from 0.899 at baseline and 0.469 from 1.004 at baseline, respectively, in the tamsulosin group relative to the naftopidil group. In the silodosin group, Spearman ρ and the slope were also decreased to 0.659 from 0.889 at baseline and 0.305 from 0.989 at baseline, respectively, relative to the naftopidil group. Naftopidil significantly increased the ratio of the frequency of mEPSCs compared to tamsulosin and silodosin (P=0.015 and P=0.004, respectively). Conclusions: There was a difference in responsiveness in the frequency of mEPSCs to α1-adrenoceptor blockers, with the response to naftopidil being the greatest among the α1-adrenoceptor blockers. These data are helpful to understand the action mechanisms of α1-adrenoceptor blockers for male lower urinary tract symptoms in clinical usage.
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Han, Jin-Wuk,Nakamura, Michiko,Choi, In-Sun,Cho, Jin-Hwa,Park, Hye-Mi,Lee, Maan-Gee,Choi, Byung-Ju,Jang, Hyun-Jung,Jang, Il-Sung Blackwell Publishing Ltd 2009 Journal of Neurochemistry Vol.109 No.4
<P>Abstract</P><P>Although it has been well established that GABA<SUB>A</SUB> receptors are molecular targets of a variety of allosteric modulators, such as benzodiazepines, the pharmacological properties of presynaptic GABA<SUB>A</SUB> receptors are poorly understood. In this study, the effects of diazepam and Zn<SUP>2+</SUP> on presynaptic GABA<SUB>A</SUB> receptors have been investigated by measuring the GABA<SUB>A</SUB> receptor-mediated facilitation of spontaneous glutamate release in mechanically dissociated rat CA3 pyramidal neurons. Diazepam significantly enhanced the muscimol-induced facilitation (particularly at submicromolar concentrations) of spontaneous glutamate release and shifted the concentration–response relationship for muscimol toward the left, whereas Zn<SUP>2+</SUP> (≤ 100 &mgr;M) had little effect on the muscimol-induced facilitation of spontaneous glutamate release. In contrast, Zn<SUP>2+</SUP> significantly suppressed the muscimol-induced currents mediated by GABA<SUB>A</SUB> receptors expressed on dentate gyrus granule cells, which are parent neurons of mossy fibers, whereas the effect of diazepam on GABA<SUB>A</SUB> receptors expressed on dentate gyrus granule cells was lesser than that on presynaptic GABA<SUB>A</SUB> receptors. The results suggest that the pharmacological properties of GABA<SUB>A</SUB> receptors differ considerably between presynaptic (axon terminals) and somatic regions in the same granule cell and that presynaptic GABA<SUB>A</SUB> receptors should be considered as one of the important pharmacological targets of many drugs affecting GABA<SUB>A</SUB> receptors.</P>
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