title: Cysteinyl leukotrienes mediate the response of submucosal ganglia from rat colon to bradykinin.
abstract: The aim of the present study was to find out the mechanism by which the inflammatory mediator, bradykinin, induces an increase of the cytosolic Ca(2+) concentration ([Ca(2+)](i)) in enteric neurons. For this purpose, ganglia in the isolated submucosa from rat colon were loaded with the Ca(2+)-sensitive dye, fura-2, and were exposed to bradykinin (2·10(-8)mol/l). Under control conditions, the kinin evoked a transient increase in [Ca(2+)](i). Preincubation with quinacrine or arachidonyltrifluoromethylketone (AACOCF(3)), i.e. blockers of cytosolic phospholipase A(2), prevented the raise of [Ca(2+)](i). This inhibition was mimicked by 5,8,11,14-eicosatetrayonic acid (ETYA), an inhibitor of cyclooxygenases as well as lipoxygenases, and by BWA4C, a selective inhibitor of lipoxygenases, whereas indomethacin was ineffective, suggesting the mediation of the kinin response by a lipoxygenase metabolite. Indeed, a leukotriene, leukotriene D(4) (LTD(4)), mimicked the effect of bradykinin. The LTD(4) receptor blocker, MK-571, inhibited the increase in [Ca(2+)](i) evoked by LTD(4) and by bradykinin. Consequently, bradykinin receptors in submucosal ganglia from rat colon are coupled to a stimulation of phospholipase A(2), the release of arachidonic acid and the production of LTD(4), which seems to be finally responsible for the change in the cytosolic Ca(2+) concentration.
authors.affiliation: Institute for Veterinary Physiology and Biochemistry, University of Giessen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Rehn
authors.forename: Martin
authors.initials: M
authors.lastname: Diener
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001095:Arachidonic Acids / Q000494:pharmacology; D001920:Bradykinin / Q000378:metabolism* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D003545:Cysteine / Q000378:metabolism*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D005260:Female; D016257:Fura-2 / Q000378:metabolism; D005724:Ganglia / Q000187:drug effects / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D017998:Leukotriene D4 / Q000378:metabolism; D015289:Leukotrienes / Q000378:metabolism*; D058945:Lipoxygenases / Q000187:drug effects / Q000378:metabolism; D054467:Phospholipases A2 / Q000378:metabolism; D011422:Propionates / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000378:metabolism; D011796:Quinacrine / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018002:Receptors, Bradykinin / Q000378:metabolism
chemical_list: D001095:Arachidonic Acids; D015289:Leukotrienes; D011422:Propionates; D011804:Quinolines; D018002:Receptors, Bradykinin; C112381:cysteinyl-leukotriene; C081565:arachidonyltrifluoromethane; D016718:Arachidonic Acid; C059141:verlukast; D017998:Leukotriene D4; D058945:Lipoxygenases; D011451:Prostaglandin-Endoperoxide Synthases; D054467:Phospholipases A2; D011796:Quinacrine; D003545:Cysteine; D001920:Bradykinin; D002118:Calcium; D016257:Fura-2