Distinct Sulfidopeptide Leukotriene Receptors
The oxidative metabolism of arachidonic acid by 5-lipoxygenase to form 5-hydro-peroxy-6-trans8-cis-eicosatetraenoic acid (5-HPETE) is followed by enzymatic conversion of 5-HPETE to 5,6-oxido-7,9-trans-ll,14-cis-eicosatetraenoic acid (LTA4). An epoxide hydrolase converts LTA4 to 5S,12R-dmydroxy-6,14-cis-8,10-trans-eicosatetraenoic acid (LTB4), whereas a glutathione-S-transferase adducts glu-tathione to yield 5S-hydroxy-6R-S-gluta.thionyl-7,9-trans-11.14-cis-eicossitrae-noic acid (LTC4). Sequential cleavages by γ-glutamyltranspeptidase of glutamic acid and by a dipeptidase of glycine form 5S-hydroxy-6R-S-cysteinylglycyl-7,9-trans-11 1,14-cis-eicosatetraenoic acid (LTD4) and 5S-hydroxy-6R-S-cysteinyl-7,9-trans-11,14-cis-eicosatetraenoic acid (LTE4), respectively. Leukotrienes C4, D4, and E4 are generically described as sulfidopeptide leukotrienes and constitute the activity previously termed slow reacting substance of anaphylaxis (Samuelsson, 1983; Lewis and Austen, 1984). The evidence indicating that the sulfidopeptide leukotrienes exert their physiological effects through interaction with several distinct receptors includes their differential functional activities on different tissues, the differential effects of pharmacological inhibitors on the agonist effects of the three sulfidopeptide leukotrienes, different receptor characteristics defined by radioligand binding studies, and apparent differences in the subcellular distribution of sulfi-dopeptide leukotriene binding sites.
KeywordsEquilibrium Dissociation Constant Plasma Membrane Fraction Radioligand Binding Study Smooth Muscle Cell Line Ileal Smooth Muscle
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