P2X receptor expression in mouse urinary bladder and the requirement of P2X(1) receptors for functional P2X receptor responses in the mouse urinary bladder smooth muscle

1 We have used subtype selective P2X receptor antibodies to determine the e xpression of P2X(1 7) receptor subunits in the mouse urinary bladder. In ad dition we have compared P2X receptor mediated responses in normal and P2X(1 ) receptor deficient mice to determine the contribution of the P2X(1) recep tor to the mouse bladder smooth muscle P2X receptor phenotype. 2 P2X(1) receptor immunoreactivity was restricted to smooth muscle of the b ladder and arteries and was predominantly associated with the extracellular membrane. Diffuse P2X(2) and P2X(4) receptor immunoreactivity not associat ed with the extracellular membrane was detected in the smooth muscle and ep ithelial layers. Immunoreactivity for the P2X(7) receptor was associated wi th the innermost epithelial layers and some diffuse staining was seen in th e smooth muscle layer. P2X(3), P2X(5) and P2X(6) receptor immunoreactivity was not detected. 3 P2X receptor mediated inward currents and contractions were abolished in bladder smooth muscle from P2X(1) receptor deficient mice. In normal bladde r nerve stimulation evoked contractions with P2X and muscarinic acetylcholi ne (mACh) receptor mediated components. In bladder from the P2X(1) receptor deficient mouse the contraction was mediated solely by mACh receptors. Con tractions to carbachol were unaffected in P2X(1) receptor deficient mice de monstrating that there had been no compensatory effect on mACh receptors. 4 These results indicate that homomeric P2X(1) receptors underlie the bladd er smooth muscle P2X receptor phenotype and suggest that mouse bladder from P2X(1) receptor deficient and normal animals may be models of human bladde r function in normal and diseased states.