Inhibition of Na+,K(+)-ATPase by platelet-activating factor in dog submandibular glands.
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 50,739, 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.
Itadani
K
K
Department of Removable Prosthodontics, Hiroshima University School of Dentistry, Japan.
Morita
K
K
Kitayama
S
S
Imai
Y
Y
Yamaki
H
H
Akagawa
Y
Y
Dohi
T
T
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001665:Binding Sites; D004285:Dogs; D008565:Membrane Proteins / Q000187:drug effects; D009077:Mucins / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D013347:Subcellular Fractions / Q000201:enzymology; D013363:Submandibular Gland / Q000201:enzymology*; D014230:Triazoles / Q000494:pharmacology
D001381:Azepines; D008565:Membrane Proteins; D009077:Mucins; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles; C039351:platelet activating factor receptor; C064509:BN 50739; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase