The mechanism of fluid secretion in the rabbit pancreas studied by means of various inhibitors.

In order to increase our understanding of the mechanism of pancreatic fluid secretion we have studied the effects of various transport inhibitors on this process in the isolated rabbit pancreas. In this preparation, a high rate of unstimulated fluid secretion occurs, which probably originates from the ductular cells. Inhibitory are ouabain, furosemide, bumetanide, piretanide, 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS) and acetazolamide, with their half-inhibitory concentrations: 2 X 10(-6) M (ouabain), 1.3 X 10(-3) M (furosemide), 2.2 X 10(-3) M (bumetanide and piretanide) and 1.4 X 10(-4) M (SITS). With acetazolamide a maximal inhibition of only 20% is found at 10(-3) M. Amiloride (10(-3) M) has no effect on pancreatic fluid secretion. The inhibitory effects on HCO-3 output are always larger and those on Cl- output lower than those on fluid secretion. The results suggest that the ouabain-sensitive (Na+ + K+)-ATPase system provides the energy for a Na+-gradient-driven Cl--HCO-3-exchange transport system, sensitive to the loop diuretics furosemide, bumetanide and piretanide and to SITS. This system would drive the transcellular transport of HCO-3 and secondarily that of cations, Cl- and water.