Angiotensin increases arachidonate metabolism in cultured anterior pituitary cells.

Angiotensin peptides produced a rapid (within 30 seconds) and concentration-dependent increase in the levels of the unesterified fatty acid and stimulated prolactin release. [3H]arachidonate appeared to be cleaved primarily from the lipid of the phosphoinositide cycle. In fact, angiotensin II produced a significant reduction of [3H]phosphatidylinositol. Conversely, [3H]diacylglycerol rapidly increased after the addition of angiotensin II to the incubation medium, returned to basal values within 2 minutes and then decreased below the control levels by 3-4 minutes, possibly due to the release of [3H]arachidonate. Finally, RHC 80267, a rather selective inhibitor of diglyceride lipase, antagonized angiotensin II-induced [3H]arachidonic acid and prolactin release. The effect of arachidonate on prolactin release has to be ascribed to further metabolism of the fatty acid to products other than prostaglandins and thromboxanes. The inhibitor of the cyclo-oxygenase pathway, indomethacin, did not significantly modify angiotensin II-induced prolactin release, whereas BW 755c and ETYA (inhibitors of cyclo-, lipo- and epoxygenase pathways) and NDGA (an inhibitor of leukotriene and epoxyeicosanoid synthesis) completely counteracted the effect of the octapeptide on hormone release.