TRPs in bladder diseases

Abstract

This review attempts to provide an overview of the current knowledge of TRP proteins and their possible role in bladder function and disease. At present, there are 28 transient receptor potential (TRP) channels (subdivided into 7 categories or families) which are involved in a number of functions [G.A. Hicks, TRP channels as therapeutic targets: hot property, or time to cool down? Neurogastroenterology and Motility 18, (2006) 590-594., J.D. Levine, N. Alessandri-Haber, TRP channels: targets for the relief of pain, Biochimica et Biophysica Acta 1772, (2007) 989-1003.]. Of those belonging to the group 1 subfamily, a number of TRPV, TRPM and TRPA proteins associated with osmoregulation, thermal, chemical and mechanical signaling mechanisms have been shown to be expressed within the lower urinary tract. Though the biological role of many of these channels in urinary bladder function still remains elusive, TRPV1 is by far the best characterized and is thought to be involved in a number of bladder disorders [A. Szallasi, P.M. Blumberg, Vanilloid (Capsaicin) Receptors and Mechanisms, Pharmacological Reviews 51, (1999) 150-221., I. Nagy, P. Santha, G. Jansco, L. Urban, The role of the vanilloid (capsaicin) receptor (TRPV1) in physiology and pathology, European Journal of Pharmacology 500, (2004) 351-369.].

Fig.1

TRPV1 is detected in urothelial cells of the rat urinary bladder. Left panel, confocal image of urinary bladder urothelium reveals TRPV1 (cy3, red) and cytokeratin (FITC, green) expression. Arrow indicates apical cells within the field from a single plane of focus. Right panel, enlarged image of basal cells depicting TRPV1 (cy3, red) and cytokeratin (FITC, green) in urothelium. Scale bar: left, 15 μm; right, 5 μm.

Fig. 2

Cystometrograms (CMGs) in anesthetized CNS-intact and unanesthetized chronic spinal rats recorded under isotonic conditions with the bladder outlet open and the animals able to void. Top panel: CMG pattern with an infusion rate of 0.052 ml/min in anesthetized CNS-intact rat. Middle panel: CMG pattern (infusion rate 0.104 ml/min) in a chronic spinal rat before capsaicin treatment. Note relatively small nonvoiding contractions occurring during bladder filling and their amplitude progressively increasing with filling (Premicturition contractions, PMC). Bottom panel: the same chronic spinal rat after capsaicin (125 mg/kg s.c.) pretreatment 4 days before the CMG study. Note the nonvoiding contractions were eliminated but the voiding contraction was not altered. Vertical calibrations: intravesical pressure in cm H₂O and horizontal calibrations: time in min. Asterisks (*) indicate voiding.