Cyclic AMP stimulation of Cl- secretion by the opercular epithelium: the basolateral chloride uptake mechanism.
The isolated, short-circuited opercular epithelium of Fundulus heteroclitus, secretes Cl- by a mechanism dependent on the presence of serosal Na+ and inhibited by bumetanide and furosemide. Under serosal Na+-free conditions the active Cl- secretion is abolished. However, subsequent elevations of intracellular cyclic AMP (cAMP) levels with isoproterenol or forskolin stimulated Cl- secretion markedly. This stimulation was unaffected by SITS, DIDS, methazolamide, and HCO-3-free solutions, but was blocked by furosemide and bumetanide. Determinations of relative intracellular 36Cl- levels showed a Na+ dependence of intracellular 36Cl- in epithelia not stimulated by isoproterenol and a Na+ independence of intracellular 36Cl- in isoproterenol stimulated epithelia. In both conditions, the intracellular 36Cl- was bumetanide sensitive. The results indicate that cAMP stimulation of Cl- secretion can occur by a Na+-independent, loop diuretic-inhibitable mechanism, which may be operative even in the presence of Na+. Whether this is a separate Cl- uptake mechanism or a cAMP-induced alteration in the normal Na+-dependent mechanism could not be determined. In either instance, an alternative to the Na+ gradient as a source of energy for Cl- uptake into the cell across the basolateral membrane is required.
D000818:Animals; D002712:Chlorides / Q000378:metabolism*; D003000:Clonidine / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology*; D003532:Cyprinodontiformes / Q000378:metabolism*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology; D007695:Killifishes / Q000378:metabolism*; D008297:Male
D002712:Chlorides; D000242:Cyclic AMP; D007545:Isoproterenol; D003000:Clonidine