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-limiting step in this process is the diffusion of Na(+) across the apical membrane of bladder epithelial cells, mediated by amiloride-sensitive epithelial Na(+) channels. We have investigated the effects of cAMP on epithelial Na(+) channel activity in the rabbit bladder by measuring the amiloride-sensitive short-circuit current across bladders mounted in Ussing chambers. Three agents that raise intracellular cAMP levels (forskolin, dibutyryl-cAMP and 3-isobutyl-1-methylxanthine (IBMX)) increased the amiloride-sensitive short-circuit current relative to control preparations. The forskolin-induced increase in amiloride-sensitive short-circuit current was significantly inhibited by the vesicle fusion inhibitor brefeldin A and the protein synthesis inhibitor cycloheximide. These findings, together with the magnitude and protracted time course of the cAMP effects, suggests that cAMP stimulates the insertion of new Na(+) channels into the apical membrane of the rabbit bladder epithelium.
Burton
T J
TJ
Department of Pharmacology, University of Cambridge, Tennis Court Road, CB2 1QJ, Cambridge, UK. tjb23@hermes.cam.ac.uk
Elneil
S
S
Nelson
C P
CP
Ferguson
D R
DR
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011817:Rabbits; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism*
D010726:Phosphodiesterase Inhibitors; D015222:Sodium Channels; D005576:Colforsin; D003994:Bucladesine; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine