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Arachidonic Acid Stimulates Intracellular Calcium Mobilization and Regulates Protein Synthesis, ATP Levels, and Mucin Secretion in Submandibular Gland Cells

Department of Oral Biology, University of Manitoba, 780 Bannatyne Avenue, Winnipeg, Manitoba, Canada R3E OW2

L. Mellow

Department of Oral Biology, University of Manitoba, 780 Bannatyne Avenue, Winnipeg, Manitoba, Canada R3E OW2

Earlier observations that arachidonic acid inhibited the synthesis of membrane inositol phospholipids in rat submandibular acinar cells prompted the present study on whether the fatty acid may also regulate other key physiological processes in the model. Arachidonate, at concentrations above 10 pmol/L, inhibited up to 97% protein synthesis in acinar cells. The acid also lowered cellular ATP levels to 25% of control values by a ouabaininsensitive mechanism. In endoplasmic reticulum-calcium studies in permeabilized cells, arachidonic acid stimulated the mobilization of up to 73% loaded ER- ⁴⁵Ca²⁺ to the cytosol, a much greater response than those caused by other calcium translocators, thapsigargin or inositol 1,4,5-trisphosphate. Additionally, arachidonate provoked the release of over 80% of total cell ⁴⁵Ca²⁺ to the extracellular space in intact cells and stimulated mucin secretion in the submandibular model. The inhibitory effect of arachidonic acid on protein synthesis was duplicated by carbachol, thapsigargin, and BAPTA/AM, three agents that cause net efflux of ER-Ca²⁺ by different mechanisms. Furthermore, comparable with the arachidonate effect on ATP, carbachol and thapsigargin also significantly reduced cellular levels of the nucleotide. It is concluded that arachidonic acid acts as a regulator of central synthetic/secretory processes in mucous acinar cells of rat submandibular gland and suggested that at least some of its effects may be secondary to its calcium-mobilizing action.

Key Words: arachidonic acid • submandibular gland • calcium mobilization • protein synthesis • ATP

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Journal of Dental Research, Vol. 74, No. 6, 1295-1302 (1995)
DOI: 10.1177/00220345950740060901


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