Endothelin stimulates short circuit current in a cultured epithelium

1. Endothelin, a novel potent vasoconstrictor peptide produced by vascular endothelial cells stimulated anion secretion by a cultured secretory epithelium derived from the rat epididymis as measured by changes in short-circuit current (SCC). 2. Stimulation of the SCC was observed when endothelin was added to the basolateral or the apical side of the epithelium. The response to basolateral application was greater than that to apical application. The EC50 values were found to be 1.3 nM and 3.0 nM for basolateral and apical application, respectively. These values were about half an order to one order of magnitude higher than that required for its vasoconstrictor action. 3. The stimulation of SCC by endothelin was accompanied by a rise in the intracellular adenosine 3':5'-cyclic monophosphate (cyclic AMP) content in epididymal monolayers. 4. The effect of endothelin on SCC was mediated through an increase in prostaglandin synthesis by the tissues and was not blocked by an antagonist of angiotensin II (Sar1 Ile8 angiotensin II) or of adrenaline (propranolol). 5. It is speculated that endogenous endothelin plays an important role in the control of water and electrolyte transport in the epididymis.