Figure 3.
The Yin – Yang system of prostanoids. Agonist stimulation of endothelial cells causes an increase in intracellular calcium levels [Ca2+]i, which releases arachidonic acid via activation of phospholipase A2 from membrane phospholipids. Alternatively, phospholipase A2 is regulated by fluid or cyclic shear stress through phosphorylation. Arachidonic acid is converted by prostaglandin endoperoxide H2 synthase (cyclooxygenase) into the intermediate prostaglandin endoperoxide H2, which is further processed into prostacyclin by prostacyclin synthase. Prostacyclin mediates vasorelaxation by acting on the prostacyclin receptor, activating adenylyl cyclase, and elevating cyclic AMP, resulting in an increase in protein kinase A activity. Furthermore, prostacyclin inhibits platelet aggregation and leukocyte adhesion to the endothelium. Under conditions that cause inhibition of prostacyclin synthase, PGH2 levels increase and PGH2 exerts thromboxane-like effects via stimulation of the thromboxane A2/PGH2 receptor. Thromboxane A2 stimulates platelet aggregation and enhances this process in an autocrine loop or promotes leukocyte adhesion. Activation of the thromboxane A2/PGH2 receptor leads to activation of phospholipase C and an increase in intracellular calcium levels. (AA = arachidonic acid; AC = adenylyl cyclase; Ag = agonist; [Ca2+]i = intracellular calcium; G = G-protein; ONOO− = peroxynitrite; •O2− = superoxide; PLA2 = phospholipase A2; •NO = nitric oxide; PGHS-1 = prostaglandin endoperoxide H2 synthase; PGH2 = prostaglandin endoperoxide H2; PGIS = prostacyclin synthase; PLC = phospholipase C; PKA = protein kinase A; Rec = receptor; TxA2 = thromboxane A2; TxAS = thromboxane synthase)