Sensitivity of cAMP-stimulated salt secretion in shark rectal gland to "loop" diuretics

Abstract

The secretory response of isolated perfused shark rectal gland was characterized with respect to its inhibition by a chemically related series of 5-sulfamoylbenzoic acid derivatives and certain phenoxyacetic acid derivatives. Maximal fluid and salt secretion was elicited with dibutyryl adenosine 3',5'-cyclic monophosphate and theophylline. The potency series established for the 5-sulfamoylbenzoic acid compounds agreed well with the relative potencies previously established for these agents as inhibitors of Na+-K+-Cl- cotransport in the avian erythrocyte. The most potent compound tested (3-benzylamino-4-phenyl-5-sulfamoylbenzoic acid) had a 50% inhibitory concentration value of approximately 5 X 10(-7) M. This compound was approximately 10-fold more effective than bumetanide and 400-fold as inhibitory as furosemide in this system. Ethacrynic acid (EA; 10(-3) M) was a poor inhibitor of rectal gland secretion and was approximately equipotent with its saturated derivative, dihydro EA. In contrast, EA-L-cysteine was fully effective at 10(-4) M, although the EA-D-cysteine adduct was ineffective. These data also qualitatively agree with results obtained in the inhibition of avian erythrocyte Na+-K+-Cl- cotransport and suggest that the rectal gland possesses a serosally oriented “NaCl cotransport” system with pharmacological and perhaps physiological similarities to the Na+-K+-Cl-cotransporter found in erythrocyte and other cell membranes.