Prostanoid biosynthesis and mechanisms of action.
Prostanoids are local hormones formed from arachidonic acid that coordinate responses to circulating hormones which elicit prostanoid synthesis. For example, in the kidney, prostaglandin (PG) E2 synthesized by collecting tubule epithelia in response to arginine vasopressin (AVP) acts on the parent collecting tubule as well as the neighboring thick limb to modulate NaCl and water reabsorption occurring in response to AVP. Studies performed over the last 15 years have defined the major cellular and subcellular sites of PG synthesis in the kidney. In addition, it is now recognized that the multiple cellular actions of prostanoids in the kidney are mediated through receptors coupled to guanine nucleotide regulatory proteins. The goal of this review is to summarize recent biochemical and molecular biological studies on prostanoid biosynthetic enzymes and on prostanoid receptors. The major topics to be addressed are 1) phospholipid precursors of arachidonate, 2) membrane-associated and cytosolic phospholipase A2s, 3) PG endoperoxide (PGH) synthase isozymes, 4) thromboxane A (TxA) synthase, and 5) TxA/PGH and PGE receptors.
Smith
W L
WL
Department of Biochemistry, Michigan State University, East Lansing 48824.
D000595:Amino Acid Sequence; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001692:Biological Transport; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism; D008969:Molecular Sequence Data; D010740:Phospholipases / Q000235:genetics / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D011498:Protein Precursors / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism
D007527:Isoenzymes; D011453:Prostaglandins; D011498:Protein Precursors; D011956:Receptors, Cell Surface; D016718:Arachidonic Acid; D011451:Prostaglandin-Endoperoxide Synthases; D010740:Phospholipases