Inhibition of Na,K-ATPase by Platelet-Activating Factor in Dog Submandibular Glands

Abstract

Physiological stimulation of dog submandibular gland has been shown to generate platelet-activating factor (PAF). However, PAF is not released from cells in the tissue. To assess its intracellular activity, the effect of PAF on Na +,K +-ATPase was examined in dog submandibular gland cells. PAF inhibited Na +,K +-ATPase in membrane preparations, and the inhibitory effect was dependent on the protein concentration in the enzyme preparation. The inhibitory effect of a low concentration of PAF was antagonized by a PAF-receptor antagonist, BN 50739, but at high concentrations, PAF was not antagonized. Kinetic analysis of PAF inhibition of Na +,K +-ATPase suggests that the inhibition of Na +,K +-ATPase by PAF is not due to competition by PAF at K +- or Na +-binding sites on the enzyme, but by complex inhibitory mechanisms. These results suggest that PAF may interact with specific and nonspecific site of action resulting in the inhibition of Na +,K +-ATPase. Ouabain increased mucin release from dog submandibular gland cells. Because Na +,K +-ATPase and ion exchange pathways are important in the secretory responses of acinar cells, PAF may regulate intracellularly the secretory function of acinar cells by modulating Na +,K +-ATPase and ionic homeostasis.