Enhancement of arachidonic acid liberation by protein kinase C activator is partially dependent on extracellular Na+ in rabbit platelets.

In [3H]arachidonic acid-labeled rabbit platelets, pretreatment with phorbol 12-myristate 13-acetate (20 nM) or dioctanoylglycerol (20 microM) enhanced [3H]arachidonic acid liberation induced by low concentration of A23187 (150 nM). When extracellular Na+ was replaced with N-methyl-D-glucamine, the enhancement is reduced by about 50%. Similar synergistic enhancement of the liberation was obtained by using monensin (2-10 microM) or NH4Cl (5-20 mM) in place of protein kinase C activator in combination with A23187. The guanosine 5'-O-[3-thiotriphosphate] (100 microM)-induced liberation was also enhanced by a rise of extracellular pH (pH 7.0-7.8) in saponin-permeabilized platelets. These results suggest that the enhancement of arachidonic acid liberation by protein kinase C may partially be mediated by intracellular alkalinization in rabbit platelets.