title: Synthesis of slow reacting substance-like activity in rabbit conjunctiva and anterior uvea.
abstract: The ability of rabbit conjunctiva and anterior uvea to synthesize lipoxygenase products was assessed. Using autoradiographic techniques, we demonstrate that rabbit anterior uvea synthesizes 5 and 12 lipoxygenase products such as 12-HETE, 5-HETE and 5,12-DiHETE and cyclooxygenase product HHT from 14C-arachidonic acid. Indomethacin pretreated conjunctiva and anterior uvea generated slow reacting substance (SRS)-like activity from arachidonic acid in the presence of reduced glutathione and A23187. This SRS-like activity contracted guinea pig ileum. Specific SRS-like activity antagonist FPL-55712 inhibited the contractions of guinea pig ileum induced by SRS-like substance generated by either conjunctiva or anterior uvea. The activity was still present in the sample following extraction with organic solvents. SRS-like activity was destroyed by arylsulfatase and its generation was prevented by either boiling or pretreatment with cyclooxygenase/lipoxygenase inhibitors, BW755 and nordihydroguaiacetic acid. These results indicate that following cyclooxygenase inhibition by indomethacin rabbit conjunctiva and anterior uvea generate SRS-like activity from arachidonic acid via lipoxygenase pathways.
mesh_terms: D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D012898:Autacoids / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D002396:Catechols / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D003228:Conjunctiva / Q000032:analysis / Q000378:metabolism*; D004789:Enzyme Activation; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D008084:Lipoxygenase / Q000378:metabolism; D016859:Lipoxygenase Inhibitors; D009637:Masoprocol; D009119:Muscle Contraction / Q000187:drug effects; D011720:Pyrazoles / Q000494:pharmacology; D011817:Rabbits; D014020:Tissue Extracts / Q000494:pharmacology; D014602:Uvea / Q000378:metabolism*
chemical_list: D001095:Arachidonic Acids; D012898:Autacoids; D002396:Catechols; D002867:Chromones; D016859:Lipoxygenase Inhibitors; D011720:Pyrazoles; D014020:Tissue Extracts; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D009637:Masoprocol; C006312:FPL 55712; D008084:Lipoxygenase