Altered permeability in the proximal tubule response to cyclic AMP

Abstract

The effects of a new analog of cyclic[c]AMP, 8-[p-chloro-phenylthio]-cAMP, on the superficial proximal convoluted tubule perfused in vitro were studied. The mechanism by which cyclic nucleotides affect proximal tubule reabsorption was studied. Transepithelial electrical potential difference, net volume reabsorption, and bath-to-lumen sucrose permeability were measured in response to a bath concentration of 10-5 M of this new cAMP analog. Changes in bath-to-lumen sucrose permeability were interpreted as indicating changes in the permeability of the paracellular pathway. This analog, 8-[p-chloro-phenylthio]-cAMP, produced a significant decrease in the lumen negative transepithelial potential difference and in net fluid reabsorption. There was a significant increase in bath-to-lumen sucrose permeability. This increase in bath-to-lumen permeability to sucrose was also observed to be independent of a decrease in net fluid reabsorption. Cyclic nucleotides inhibit proximal tubule volume reabsorption at least in part by increasing the permeability of the paracellular pathway. Such a change in permeability may allow for increased backleak of reabsorbate and a resulting decrease in net volume reabsorption.