Arachidonic acid stimulates intracellular calcium mobilization and regulates protein synthesis, ATP levels, and mucin secretion in submandibular gland cells.
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 mumol/L, inhibited up to 97% protein synthesis in acinar cells. The acid also lowered cellular ATP levels to 25% of control values by a ouabain-insensitive 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.
Fleming
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Department of Oral Biology, University of Manitoba, Winnipeg, Canada.
Mellow
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L
D000255:Adenosine Triphosphate / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D016718:Arachidonic Acid / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002463:Cell Membrane Permeability; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000378:metabolism; D066298:In Vitro Techniques; D017136:Ion Transport; D008297:Male; D009077:Mucins / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism; D014176:Protein Biosynthesis / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012471:Salivary Proteins and Peptides / Q000096:biosynthesis*; D018709:Statistics, Nonparametric; D013363:Submandibular Gland / Q000378:metabolism*
D009077:Mucins; D012471:Salivary Proteins and Peptides; D016718:Arachidonic Acid; D000255:Adenosine Triphosphate; D004247:DNA; D010741:Phospholipases A; D000252:Calcium-Transporting ATPases; D002118:Calcium