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Functional Role of the Transient Receptor Potential Melastatin 8 (TRPM8) Ion Channel in the Urinary Bladder Assessed by Conscious Cystometry and Ex Vivo Measurements of Single-Unit Mechanosensitive Bladder Afferent Activities in the Rat

Functional Role of the Transient Receptor Potential Melastatin 8 (TRPM8) Ion Channel in the Urinary Bladder Assessed by Conscious Cystometry and Ex Vivo Measurements of Single-Unit Mechanosensitive Bladder Afferent Activities in the Rat

Hiroki Ito, Naoki Aizawa, Rino Sugiyama, Shuzo Watanabe, Nobuyuki Takahashi, Masaomi Tajimi, Hiroshi Fukuhara, Yukio Homma, Yoshinobu Kubota, Karl-Erik Andersson, Yasuhiko Igawa

BJU Int. 2016 Mar;117(3):484-94.

PMID: 26189966

Abstract:

Objective:
To evaluate the role of the transient receptor potential melastatin 8 (TRPM8) channel on bladder mechanosensory function by using L-menthol, a TRPM8 agonist, and RQ-00203078 (RQ), a selective TRPM8 antagonist.
Materials and methods:
Female Sprague-Dawley rats were used. In conscious cystometry (CMG), the effects of intravesical instillation of L-menthol (3 mm) were recorded after intravenous (i.v.) pretreatment with RQ (3 mg/kg) or vehicle. The direct effects of RQ on conscious CMG and deep body temperature were evaluated with cumulative i.v. administrations of RQ at 0.3, 1, and 3mg/kg. Single-unit mechanosensitive bladder afferent activities (SAAs) were monitored in a newly established ex vivo rat bladder model to avoid systemic influences of the drugs. Recordings were performed after cumulative intra-aortic administration of RQ (0.3 and 3 mg/kg) with or without intra-vesical L-menthol instillation (3 mm).
Results:
Intravesical L-menthol decreased bladder capacity and voided volume, which was counteracted by RQ-pretreatment. RQ itself increased bladder capacity and voided volume, and lowered deep body temperature in a dose-dependent manner. RQ decreased mechanosensitive SAAs of C-fibres, and inhibited the activation of SAAs induced by intravesical L-menthol.
Conclusion:
Our results suggest that TRPM8 channels have a role in activation of bladder afferent pathways during filling of the bladder in the normal rat. This effect seems, at least partly, to be mediated via mechanosensitive C-fibres.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1254205521	RQ-00203078		1254205-52-1	Price

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