Studies on the mechanism of inhibition of sodium transport in cystic fibrosis of the pancreas.

Abstract

Extract: The saliva of patients with cystic fibrosis of the pancreas (CFP) contains a factor that inhibits sodium reabsorption in the rat parotid gland. The possibility that this factor is a strongly basic macromolicular substance was investigated. Basic polyelectrolytes in interact electrostatically with the negatively charged surface of the membrane of a variety of living cells and affect membrane structure and function. Retrograde perfusion of the duct system of the rat parotid was used to study the effect of two natural and three synthetic basic polyelectrolytes on the sodium reabsorption in the rat parotid. Interaction of the liminal side of the parotid duct system with dilute solutions of protamine surface, polyethylene imine, arginine-rich histone, polysysine, and polyornithine resulted in significant inhibition of the transductal reabsorption of sodium. Addition of heparin, a strongly negatively charged protein, to the solutions containing the above basic polyelectrolytes resulted in complete elimination of sodium transport inhibitory activity, possibly due to electrostatic interaction and percipitation. Similarly, addition of heparin to the 4:1 mixture of aline and saliva from patients with CFP dliminated sodium transport inhibitory activity. It was concluded that the sodium transport inhibitory factor of CFP may be a strongly basic macromolecule that interacts with the cell membrane of transporting epithelia and causes a defect in the reabsorption of sodium in exocring glands.Speculation: Sodium transport inhibition has been demonstrated in the rat parotid gland following interaction of the luminal side of the duct system with dilute solutions of natural or systhetic basic polyelectrolytes. This activity of the above solutions disappears following the addition of heparin, a negatively charged protein. Similarly, heparin eliminates the sodium transport inhibitory activity of saliva from patients with CFP. This, admittedly indirect, evidence suggests that the sodium transport inhibitory factor in the saliva of patients with CFP may be a strongly basic macromolocule and opens new directions in the search for the molecular defect of CFP.