title: Microcystin-induced activation of prostaglandin synthesis and phospholipid metabolism in rat hepatocytes.
abstract: The effects of microcystin-LR, a trichothecene, T-2 and saxitoxin on membrane lipid mediators of inflammatory processes were evaluated in cultured rat hepatocytes using [(14)C]arachidonic acid. Microcystin-LR significantly stimulated the release of prostacyclin, measured as 6-keto PGF(1)alpha, by 38%, and thromboxane B(2) by 50%, in a concentration-dependent manner. The trichothecene toxin T-2 enhanced the release of prostaglandin F(2)alpha by 24% and arachidonic acid by 29%; while saxitoxin did not affect the release prostaglandins or arachidonic acid. Incorporation of arachidonic acid into the lipid pool was reduced by 47% by 1 mum microcystin-LR. Changes in the distribution of radioactivity derived from [(14)C]arachidonic acid within phospholipid classes indicated that prostaglandin formation induced by microcystin-LR was also due to the release of arachidonic acid from the phosphatidylinositol pool. No statistically significant effect of toxin was observed on the contribution of [(14)C]arachidonic acid release by other classes of phospholipids or neutral lipids. These effects may be important in the mechanism of microcystin-LR-induced toxicity in the liver.
authors: Pathophysiology Division, US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702-5011, USA.
authors: S M
authors: SM
authors: Naseem
authors: K A
authors: KA
authors: Mereish
authors: R
authors: R
authors: Solow
authors: H B
authors: HB
authors: Hines