Activation of epithelial Na+ channel activity in the rabbit urinary bladder by cAMP

The rabbit urinary bladder actively absorbs Na+ from the urine. The rate-li miting step in this process is the diffusion of Na+ across the apical membr ane of bladder epithelial cells, mediated by amiloride-sensitive epithelial Na+ channels. We have investigated the effects of cAMP on epithelial Na+ c hannel activity in the rabbit bladder by measuring the amiloride-sensitive short-circuit current across bladders mounted in Ussing chambers. Three age nts that raise intracellular cAMP levels (forskolin, dibutyryl-cAMP and 3-i sobutyl-1-methylxanthine (IBMX)) increased the amiloride-sensitive short-ci rcuit current relative to control preparations. The forskolin-induced incre ase in amiloride-sensitive short-circuit current was significantly inhibite d by the vesicle fusion inhibitor brefeldin A and the protein synthesis inh ibitor cycloheximide. These findings, together with the magnitude and protr acted time course of the cAMP effects, suggests that cAMP stimulates the in sertion of new Na+ channels into the apical membrane of the rabbit bladder epithelium. (C) 2000 Elsevier Science B.V. All rights reserved.