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This Article Full Text Full Text (PDF) All Versions of this Article: 294/4/F821    most recent 00321.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Chopra, B. Articles by Birder, L. A. PubMed PubMed Citation Articles by Chopra, B. Articles by Birder, L. A.

Expression and function of rat urothelial P2Y receptors

Departments of ¹Medicine and ²Pharmacology, University of Pittsburgh, Pittsburgh, Pennsylvania; and ³Roche, Biochemical Pharmacology Group, Inflammation Discovery, Palo Alto, California

Submitted 12 August 2006 ; accepted in final form 17 January 2008

The control and regulation of the lower urinary tract are partly mediated by purinergic signaling. This study investigated the distribution and function of P2Y receptors in the rat urinary bladder. Application of P2Y agonists to rat urothelial cells evoked increases in intracellular calcium; the rank order of agonist potency (pEC₅₀ ± SE) was ATP (5.10 ± 0.07) > UTP (4.91 ± 0.14) > UTPS (4.61 ± 0.16) = ATPS (4.70 ± 0.05) > 2-methylthio adenosine 5'-diphosphate = 5'-(N-ethylcarboxamido)adenosine = ADP (<3.5). The rank order potency for these agonists indicates that urothelial cells functionally express P2Y₂/P2Y₄ receptors, with a relative lack of contribution from other P2Y or adenosine receptors. Real-time PCR, Western blotting, and immunocytochemistry confirmed the expression of P2Y₂ and to a lesser extent P2Y₄ in the urothelium. Immunocytochemical studies revealed expression of P2Y₂ staining in all layers of the urothelium, with relative absence of P2Y₄. P2Y₂ staining was also present in suburothelial nerve bundles and underlying detrusor smooth muscle. Addition of UTP and UTPS was found to evoke ATP release from cultured rat urothelial cells. These findings indicate that cultured rat urothelial cells functionally express P2Y₂/P2Y₄ receptors. Activation of these receptors could have a role in autocrine and paracrine signaling throughout the urothelium. This could lead to the release of bioactive mediators such as additional ATP, nitric oxide, and acetylcholine, which can modulate the micturition reflex by acting on suburothelial myofibroblasts and/or pelvic afferent fibers.

purinergic receptors; urinary bladder; epithelium; lower urinary tract