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Neurourol Urodyn. 2018 Jun;37(5):1541-1548. doi: 10.1002/nau.23423. Epub 2018 Mar 22.

Tadalafil attenuates hypotonicity-induced Ca2+ influx via TRPV2 and TRPV4 in primary rat bladder urothelial cell cultures.

Author information

1
Department of Urology, the First Hospital of China Medical University, Shenyang, People's Republic of China.
2
Department of Urology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi 1110 Shimokato, Chuo, Yamanashi, Japan.

Abstract

AIMS:

To investigate the localization of phosphodiesterase 5 (PDE5) and the molecular mechanism underlying the effect of the PDE5 inhibitor tadalafil in signal transduction in the bladder urothelium.

METHODS:

PDE5 expression in rat bladder tissues and cultured primary rat bladder urothelial cells was evaluated using immunochemistry and western blot assays. Ca2+ influx in cells exposed to isotonic solution, hypotonic solution, a selective transient receptor potential vanilloid 2 (TRPV2) channel agonist (cannabidiol), a selective TRPV4 channel agonist (GSK1016790A), a TRP cation channel melastatin 7 (TRPM7) channel agonist (PIP2), or a purinergic receptor agonist (ATP) in the presence or absence of 10 µM tadalafil was evaluated using calcium imaging techniques. We also evaluated stretch-induced changes in ATP concentration in the mouse bladder in the presence or absence of 100 µM tadalafil.

RESULTS:

Immunochemistry and western blot analyses demonstrated that PDE5 is abundantly expressed in the bladder urothelium and in primary rat urothelial cells. Ca2+ influx induced by hypotonic stimulation, GSK1016790A, or cannabidiol was significantly inhibited by tadalafil, whereas ATP-induced Ca2+ influx was unaffected by tadalafil. PIP2 did not induce Ca2+ influx. ATP release in tadalafil-pretreated bladders significantly decreased compared to control bladders.

CONCLUSIONS:

Tadalafil attenuates Ca2+ influx via TRPV4 and TRPV2, and inhibits ATP release in the bladder urothelium. These findings indicate that tadalafil functions as an inhibitor of urothelial signal transduction.

KEYWORDS:

ATP; TRP channel; lower urinary tract symptoms; phosphodiesterase type 5; tadalafil

PMID:
29566267
DOI:
10.1002/nau.23423
[Indexed for MEDLINE]

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