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      Prostanoid Receptors: Structures, Properties, and Functions

      1 , 1 , 1

      Physiological Reviews

      American Physiological Society

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          Abstract

          Prostanoids are the cyclooxygenase metabolites of arachidonic acid and include prostaglandin (PG) D 2, PGE 2, PGF , PGI 2, and thromboxne A 2. They are synthesized and released upon cell stimulation and act on cells in the vicinity of their synthesis to exert their actions. Receptors mediating the actions of prostanoids were recently identified and cloned. They are G protein-coupled receptors with seven transmembrane domains. There are eight types and subtypes of prostanoid receptors that are encoded by different genes but as a whole constitute a subfamily in the superfamily of the rhodopsin-type receptors. Each of the receptors was expressed in cultured cells, and its ligand-binding properties and signal transduction pathways were characterized. Moreover, domains and amino acid residues conferring the specificities of ligand binding and signal transduction are being clarified. Information also is accumulating as to the distribution of these receptors in the body. It is also becoming clear for some types of receptors how expression of their genes is regulated. Furthermore, the gene for each of the eight types of prostanoid receptor has been disrupted, and mice deficient in each type of receptor are being examined to identify and assess the roles played by each receptor under various physiological and pathophysiological conditions. In this article, we summarize these findings and attempt to give an overview of the current status of research on the prostanoid receptors.

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          Most cited references 178

          • Record: found
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          Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs.

           J R Vane (1971)
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            Hypertension in mice lacking the gene for endothelial nitric oxide synthase.

            Nitric oxide (NO), a potent vasodilator produced by endothelial cells, is thought to be the endothelium-dependent relaxing factor (EDRF) which mediates vascular relaxation in response to acetylcholine, bradykinin and substance P in many vascular beds. NO has been implicated in the regulation of blood pressure and regional blood flow, and also affects vascular smooth-muscle proliferation and inhibits platelet aggregation and leukocyte adhesion. Abnormalities in endothelial production of NO occur in atherosclerosis, diabetes and hypertension. Pharmacological blockade of NO production with arginine analogues such as L-nitroarginine (L-NA) or L-N-arginine methyl ester affects multiple isoforms of nitric oxide synthase (NOS), and so cannot distinguish their physiological roles. To study the role of endothelial NOS (eNOS) in vascular function, we disrupted the gene encoding eNOS in mice. Endothelium-derived relaxing factor activity, as assayed by acetylcholine-induced relaxation, is absent, and the eNOS mutant mice are hypertensive. Thus eNOS mediates basal vasodilation. Responses to NOS blockade in the mutant mice suggest that non-endothelial isoforms of NOS may be involved in maintaining blood pressure.
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              A G-protein-coupled receptor for leukotriene B4 that mediates chemotaxis.

              Leukotriene B4 (LTB4) is a potent chemoattractant that is primarily involved in inflammation, immune responses and host defence against infection. LTB4 activates inflammatory cells by binding to its cell-surface receptor (BLTR). LTB4 can also bind and activate the intranudear transcription factor PPAR alpha, resulting in the activation of genes that terminate inflammatory processes. Here we report the cloning of the complementary DNA encoding a cell-surface LTB4 receptor that is highly expressed in human leukocytes. Using a subtraction strategy, we isolated two cDNA clones (HL-1 and HL-5) from retinoic acid-differentiated HL-60 cells. These two clones contain identical open reading frames encoding a protein of 352 amino acids and predicted to contain seven membrane-spanning domains, but different 5'-untranslated regions. Membrane fractions of Cos-7 cells transfected with an expression construct containing the open reading frame of HL-5 showed specific LTB4 binding, with a K(d) (0.154nM) comparable to that observed in retinoic acid-differentiated HL-60 cells. In CHO cells stably expressing this receptor, LTB4 induced increases in intracellular calcium, D-myo-inositol-1,4,5-triphosphate (InsP3) accumulation, and inhibition of adenylyl cyclase. Furthermore, CHO cells expressing exogenous BLTR showed marked chemotactic responses towards low concentrations of LTB4 in a pertussis-toxin-sensitive manner. Our findings, together with previous reports, show that LTB4 is a unique lipid mediator that interacts with both cell-surface and nuclear receptors.
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                Author and article information

                Journal
                Physiological Reviews
                Physiological Reviews
                American Physiological Society
                0031-9333
                1522-1210
                January 10 1999
                January 10 1999
                : 79
                : 4
                : 1193-1226
                Affiliations
                [1 ]Department of Pharmacology, Kyoto University Faculty of Medicine, and Department of Physiological Chemistry, Kyoto University Faculty of Pharmaceutical Sciences, Kyoto, Japan
                Article
                10.1152/physrev.1999.79.4.1193
                10508233
                © 1999

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