ENDOTHELIN-1 STIMULATES CHLORIDE AND POTASSIUM SECRETION IN RABBIT DESCENDING COLON

The vasoactive peptide endothelin-1 (ET-1) which is present in high concentrations in the colon, causes concentration-dependent electrogenic Cl- secretion in rabbit descending colon. This effect is half-maximal at 0.11-mu-mol/l. Like other secretagogues, ET-1 also stimulates K+ secretion. The secretory effect of ET-1 is associated with increased release of prostaglandin E2 from the serosal surface of the mucosa. ET-1-induced Cl- secretion is completely inhibited by the loop diuretic bumetanide and by indomethacin and quinacrine, inhibitors of prostaglandin synthesis. Neuronal mechanisms do not seem to be involved, as tetrodotoxin did not affect the secretory response to ET-1 significantly. On the other hand, neither the catalytic activity nor the transport function of the Na+/K+-ATPase of rabbit colon epithelium is affected by endothelin-1 (ET-1) in concentrations up to 10-mu-mol/l. It is concluded that ET-1 causes Cl- and K+ secretion by stimulating phospholipase A2 and release of prostaglandins, whereas Na+ transport is not altered.