Journal of Dental Research, Vol 71, 1462-1467, Copyright © 1992 by International & American Associations for Dental Research Online Journals
Arachidonic acid regulates the phosphoinositide signal transduction pathway in submandibular acinar cells
H. C. Chung and N. Fleming
Department of Oral Biology, Faculty of Dentistry, University of Manitoba, Winnipeg.
Modulation of the phosphoinositide signal transduction pathway by
arachidonic acid (AA) in collagenase-dispersed rat submandibular acinar
cells was investigated. The muscarinic agonist, carbachol, stimulated PIP2
hydrolysis and the generation of IP3 to five-fold the control levels. This
response was inhibited by 75% on pre-treatment of cells with AA. The AA
inhibitory effect was not duplicated by a range of prostaglandins and
leukotrienes and was not reversed by blockers of the cyclo-oxygenase and
lipoxygenase synthetic pathways, indicating that AA action was not mediated
by eicosanoid metabolites. Additional experiments confirmed that the
enzyme, protein kinase C, was also not a mediator of the AA effect.
Arachidonic acid did not affect the uptake of radioactive inositol into
acinar cells, but it did inhibit the incorporation of inositol into
inositol phospholipids of the phosphoinositide cycle. In studies on
inositol phospholipid turnover, AA alone reduced the level of PIP2 but not
of PIP or PI. Under conditions of PI cycle stimulation with carbachol, AA
significantly lowered PIP2 and PIP but not PI. These findings suggest that
arachidonic acid may regulate the phosphoinositide response by inhibiting
the synthetic phase of the cycle at a locus distal to PI generation.
