Isolation and characterization of 9‐hydroxy‐10‐trans,12‐cis‐octadecadienoic acid, a novel regulator of platelet adenylate cyclase from Glechoma hederacea L. Labiatae

Abstract

We have identified and characterized a fatty acid, (9S,10E,12Z)‐9‐hydroxy‐10,12‐octadecadienoic acid (9‐HODE) as a regulator of adenylate cyclase activity of human platelet membranes. This fatty acid was isolated from a methanolic extract of the plant Glechoma hederacea L. Labiatae (commonly known as ‘lierre terrestre’, ‘ground ivy’ or ‘creeping Charlie’; it was identified by nuclear magnetic resonance and mass spectroscopy. This compound increased basal adenylate cyclase activity in platelet membranes about threefold and had an EC50 of 10–20μM. This increase in adenylate cyclase activity occurred without a temporal lag, was reversible, and represented an increase in Vmax without a substantial change in Km for ATP, Mg2+ or Mn2+. In addition, 9‐HODE additively or synergistically increased platelet adenylate cyclase activity in response to guanosine 5′‐[β,γ‐imido]triphosphate and forskolin, but the fatty acid failed to alter inhibition of adenylate cyclase activity mediated by epinephrine (α2‐adrenergic receptor). Studies of the interaction of 9‐HODE with activation of platelet adenylate cyclase activity mediated by prostaglandin El (PGE1) and prostaglandin D2 (PGD2) indicated that this fatty acid produced a parallel shift in the concentration/response curve of PGE1 and PGD2 without altering maximal response, which was substantially greater than that observed with 9‐HODE alone. From these results, we conclude that 9‐HODE appears to be a partial agonist at PGE1 and PGD2 receptors on human platelets. We believe that this is a novel example of a plant‐derived fatty acid which acts on cells to regulate adenylate cyclase via prostaglandin receptors. Copyright © 1987, Wiley Blackwell. All rights reserved