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. 2019 Mar;23(1):13-21.
doi: 10.5213/inj.1938056.028. Epub 2019 Mar 31.

Characterization on Responsiveness of Excitatory Synaptic Transmissions to α1-Adrenoceptor Blockers in Substantia Gelatinosa Neurons Isolated From Lumbo-Sacral Level in Rat Spinal Cords

Daisuke Uta  1   2 , Tsuyoshi Hattori  3 , Megumu Yoshimura  2   4   5
Affiliations

Characterization on Responsiveness of Excitatory Synaptic Transmissions to α1-Adrenoceptor Blockers in Substantia Gelatinosa Neurons Isolated From Lumbo-Sacral Level in Rat Spinal Cords

Daisuke Uta et al. Int Neurourol J. 2019 Mar.

Abstract

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).

Conclusion: 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.

Keywords: Adrenergic alpha1 antagonists; Excitatory postsynaptic currents; Naftopidil; Substantia gelatinosa.

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Conflict of interest statement

Conflict of Interest

This study was also supported in part by the Asahi Kasei Pharma Corporation. Except for that, no potential conflict of interest relevant to this article was reported.

Figures

Fig. 1.
Fig. 1.
The experimental method and design are illustrated. (A) Blind whole-cell patch-clamp recording is set in a substantia gelatinosa (SG) neuron of an adult rat spinal dorsal horn. (B) In a single neuron, three α1-adrenoceptor blockers are evaluated sequentially with wash-out periods.
Fig. 2.
Fig. 2.
Correlations of the frequencies of miniature excitatory postsynaptic current at baseline. (A) Before naftopidil treatment vs. before tamsulosin treatment. (B) Before naftopidil treatment vs. before silodosin treatment. N=36.
Fig. 3.
Fig. 3.
The effects of α1-adrenoceptor blockers on miniature excitatory postsynaptic current (mEPSCs). (A-C) Typical charts presenting the responses to three α1-adrenoceptor blockers, response to no α1-adrenoceptor blockers, and response to only naftopidil, respectively. Color bars show durations of drugs. (D, E) Correlation of the frequencies of mEPSCs after naftopidil and tamsulosin treatment, and after naftopidil and silodosin treatment, respectively. N=36.
Fig. 4.
Fig. 4.
Ratios of the frequencies after to before treatment. *Compared with naftopidil.
Fig. 5.
Fig. 5.
The ratios of posttreatment with each α1-adrenoceptor blocker to baseline for the frequencies of miniature excitatory postsynaptic current (mEPSCs). SG, substantia gelatinosa.
Fig. 6.
Fig. 6.
Summary of the responsiveness of the frequencies of miniature excitatory postsynaptic current to α1-adrenoceptor blockers.
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