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<p>The lower urinary tract stores and periodically eliminates urine, which is regulated by the peripheral and central nervous system (CNS). Thromboxane A₂ (TxA<sub>2</sub>), an arachidonic acid metabolite known for platelet aggregation, is a neuromodulator exciting the glutamatergic nervous system, which is essential for the voiding function in the CNS. However, roles of brain TxA<sub>2</sub> in regulating micturition reflex remain unclear. Therefore, we investigated the effects of (1) centrally administered TxA<sub>2</sub> analogue U-46619 on the reflex, and (2) centrally pretreated TxA<sub>2</sub> receptor (TP receptor) and glutamate receptor antagonists on analogue-induced responses in male rats. Under urethane anaesthesia, centrally administered U-46619 [10 nmol per rat, intracerebroventricularly (ICV)] significantly shortened intercontraction interval (ICI), the interval between two bladder voiding contractions. Additionally, U-46619 (10 nmol per rat, ICV) reduced the single-voided volume and bladder capacity without altering post-voided residual volume or voiding efficacy. However, the U-46619-induced ICI shortening was suppressed by pretreatment with S-18886 (TP receptor antagonist, 300 nmol per rat, ICV), or DNQX (α-amino-3-hydroxy-5-methyl-4-isoxazole propionate [AMPA] glutamate receptor antagonist, 3 nmol per rat, ICV). From these results, stimulation of brain TP receptors facilitates the micturition reflex through brain AMPA receptors. We propose a novel function of brain TxA<sub>2</sub> in the micturition regulation.</p>

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Centrally administered thromboxane A2 analogue facilitates the micturition reflex in rats

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月28日

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  • Chisato Hamada,
  • Takahiro Shimizu,
  • Mio Togo,
  • Youichirou Higashi,
  • Nobutaka Shimizu,
  • Junichi Furumiya,
  • Motoaki Saito

摘要

The lower urinary tract stores and periodically eliminates urine, which is regulated by the peripheral and central nervous system (CNS). Thromboxane A₂ (TxA2), an arachidonic acid metabolite known for platelet aggregation, is a neuromodulator exciting the glutamatergic nervous system, which is essential for the voiding function in the CNS. However, roles of brain TxA2 in regulating micturition reflex remain unclear. Therefore, we investigated the effects of (1) centrally administered TxA2 analogue U-46619 on the reflex, and (2) centrally pretreated TxA2 receptor (TP receptor) and glutamate receptor antagonists on analogue-induced responses in male rats. Under urethane anaesthesia, centrally administered U-46619 [10 nmol per rat, intracerebroventricularly (ICV)] significantly shortened intercontraction interval (ICI), the interval between two bladder voiding contractions. Additionally, U-46619 (10 nmol per rat, ICV) reduced the single-voided volume and bladder capacity without altering post-voided residual volume or voiding efficacy. However, the U-46619-induced ICI shortening was suppressed by pretreatment with S-18886 (TP receptor antagonist, 300 nmol per rat, ICV), or DNQX (α-amino-3-hydroxy-5-methyl-4-isoxazole propionate [AMPA] glutamate receptor antagonist, 3 nmol per rat, ICV). From these results, stimulation of brain TP receptors facilitates the micturition reflex through brain AMPA receptors. We propose a novel function of brain TxA2 in the micturition regulation.