EICOSANOIDS vol. 20 Ei Eicosanoids 800.364.9897 www.caymanchem.com Introduction to Eicosanoids Paper wasps, as shown on the cover, are representative of stinging insects in that their sting injects a venom containing a mixture of bioactive compounds. However, the venom of vespids (wasps, hornets) differs from that of other insects, including the apids (honey bees, bumble bees). Vespid venom includes histamine, which causes swelling, pain, and itching, as well as components which stimulate mast cells to release histamine and the eicosanoids prostaglandin D2 and leukotriene C4. These bioactive lipids drive bronchoconstriction and edema, meaning that the wasp sting can be lethal if it occurs near the throat. Moreover, these mediators, with other components in wasp venom, contribute to the development of an allergic response. Sensitization to wasp venom can occur after a single sting, presenting the possibility of a potentially life-threatening anaphylactic reaction at some later date. The venom of bees contrasts with that of the wasp in that it contains abundant melittin, a peptide which directly associates with cellular membranes and stimulates the action of cytosolic phospholipase A2 (cPLA2). As described on page 48 of this catalog, cPLA2 plays a critical role in the release of arachidonic acid for the generation of eicosanoids. Bee venom also includes a small (19 kDa) PLA2, unique to bees, which contributes to an allergic response. However, allergy to bee venom requires being stung frequently by bees and, as a result, is less common than sensitivity to wasp stings. Notably, individuals who are allergic to wasp venom are rarely allergic to bee venom. The roles for eicosanoids in insect stings are indicative of the diversity of actions for these bioactive lipids. Cayman invites you to learn more about eicosanoids by offering you topical updates in this catalog. Of course, we are also creating a buzz by offering the latest reagents and assay kits for eicosanoid research. In addition, Cayman performs cGMP production of prostaglandins for human and veterinarian use; some of these active pharmaceutical ingredients are profiled in an article on page 28. To help make your research possible, we also offer our expertise and facilities through our Contract Services, where we analyze your samples, run your samples in our assays, and perform custom chemical syntheses. Visit our website, caymanchem.com, or call us to find out how we can work together to further your understanding of eicosanoids. [Ordering Information] [Table of Contents] EICOSANOIDS 2 2013 VOLUME 20 EICOSANOIDS 3 2013 VOLUME 20 Cayman Chemical www.caymanchem.com Cayman Chemical www.caymanchem.com Eicosanoids Leukotrienes – Something Old, Something New 4 Thomas G. Brock, Ph.D. [Products] 6 Biochemicals EP2 and EP4, Sibling PGE2 Receptors 16 Thomas G. Brock, Ph.D. APIs – Prostaglandins with a Purpose 28 Thomas G. Brock, Ph.D. Hypertension and Eicosanoids Ordering Information 38 Thomas G. Brock, Ph.D. Intracellular PLA2 activation and Orders are accepted by telephone, fax, mail, e-mail, or via the Cayman Chemical website. We will accept Use of Research Products functional cooperation telephone orders Monday through Friday from 8 AM to 6 PM EST. All orders received by 1 PM EST will be The products in this catalog are not for human or veterinary disease diagnosis or therapeutic drug use. They shipped the same day if stock is available (Monday through Thursday only). Confirming purchase orders should be used only by technically qualified individuals or those under their direct supervision. Any individual Olivia L. 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For current US pricing see www.caymanchem.com. For current European or other overseas pricing, see www.caymaneurope.com or contact your local distributor. [Article: Leukotrienes – Something Old, Something New] Figure 2. Following focal injury (dotted circle, left), scout neutrophils rapidly migrate from capillaries to the damage site (center). Subsequent swarming and clustering of additional neutrophils is mediated by LTB4. LEUKOTRIENES Something Old • Something New Injury Localized Response Swarming Response case for EIB, CysLT receptor antagonists are useful in treating experimental purinergic receptors and GPR99 shares features with P2Y1 receptors, although Dengue Virus infection. Also, the production of CysLTs in asthma may be it is not in that subfamily.25 That is, it remains possible that GPR99 dimerizes 16 regulated by a novel secreted phospholipase A2 (sPLA2-X). This enzyme, with another unidentified protein, the true receptor for LTE4. The authors which is released from epithelial cells, is increased in the airways of patients with are careful not to over-interpret their data; however, it seems reasonable to EIB and initiates eicosanoid synthesis in target cells, including eosinophils. anticipate that GPR99 will prove to be a third CysLT receptor. n Primary Ligands by [Thomas G. Brock, Ph.D.] LTs in Your Head Receptor Alternative Names Ligands (binding affinity) Broadly speaking, LTB4 is produced by neutrophils and drives inflammation, LTB (0.154 nM), ATP in the form of leukocyte recruitment, while CysLTs, key mediators generated BLT LTB4R1, P2Y7, GPR16 LTB > ATP >> UTP = ADP 4 Leukotrienes (LTs) are well-known lipid mediators.