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ATP related to VNUT maintains the normal bladder storage function

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Sources of Funding: none

Introduction

ATP is an important substance in bladder function. Vesicular Nucleotide Transporter (VNUT) involved in exocytosis of ATP strongly expressed in the bladder urothelium. VNUT Knock out (KO) mice show frequent urination without a change in voiding function. One of the causes is the reduction of bladder compliance which based on the difficulty of the bladder urothelium surface area expansion. However all mechanism is unclear, here we underwent organ bath studies._x000D_

Methods

All experiments were performed by using 8-14 week old male C57BL/6 mice (WT) and VNUTKO mice backcrossed (for eight generations) on a C57BL/6 background. Bladder strips (with or without urothelium) were subjected to a resting tension of 1 g and allowed to stabilize for at least 30 min. Contractions were recorded as changes in tension from baseline in response to 60 mM KCl, carbachol, and electrical field stimulation (EFS). All tissue responses were normalized to gram tissue weight.

Results

The bladder without urothelium from VNUTKO mice showed a higher contractile response to 60 mM KCl compared with WT, but no change between bladders with urothelium. There was no difference in contractions by carbachol between WT and VNUTKO bladders with the presence of urothelium (Fig1). In the absence of urothelium, the responses to carbachol (Fig1) and EFS were higher in VNUTKO mice than WT mice.

Conclusions

The contraction of bladder smooth muscle in VNUTKO mice was strongly enhanced that may show the pathological state. Exocytotic ATP released from urothelium could maintain the normal bladder storage function.

Funding

none

Authors
Hiroshi Nakagomi
Tatsuya Miyamoto
Tatsuya Ihara
Satoru Kira
Norifumi Sawada
Takahiko Mitsui
Schuichi Koizumi
Masayuki Takeda
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