4.3 Article

TRPM8 agonists modulate contraction of the pig urinary bladder

Journal

CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
Volume 91, Issue 7, Pages 503-509

Publisher

CANADIAN SCIENCE PUBLISHING, NRC RESEARCH PRESS
DOI: 10.1139/cjpp-2012-0406

Keywords

pig; isolated bladder; urothelium; detrusor; TRPM8; icilin; menthol

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The transient receptor potential melastin-8 (TRPM8) channel is activated by the cooling compounds menthol and icilin. Pathophysiologically, it is implicated in the overactive bladder and bladder cooling reflex, but the activity of TRPM8 in normal bladder physiology is poorly understood. We investigated the distribution of TRPM8 channels and the effect of TRPM8 agonists on the contractile function of pig bladder (n = 35) strips and whole bladders. The distribution of TRPM8 was examined by immunohistochemistry. The effect of vesical or intravascular menthol (0.1-0.3 mmol/L) or icilin (50 mu mol/L) on carbachol-induced isolated whole bladder contractions was monitored by recording vesical pressure. Strips of denuded detrusor or mucosa were mounted in organ baths to study the effect of TRPM8 agonists on the contractile responses to 10 mu mol/L carbachol. TRPM8-like immunoreactivity was detected on pig urothelium. Intravascular menthol (0.3 mmol/L) and icilin (50 mu mol/L) significantly decreased the magnitude of carbachol-induced whole bladder contraction, whereas vesical administration significantly increased the response. In detrusor and mucosal strips, both menthol (0.3 mmol/L) and icilin (50 mu mol/L) inhibited carbachol-induced contractions. We conclude that the TRPM8 channel is expressed on the urothelium of pig bladder. In the whole organ, exposure of the urothelium to menthol or icilin increases the contractile response to carbachol. Where detrusor muscle is exposed directly to these compounds, the contractile response to carbachol is reduced.

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