title: Bradykinin regulates cyclooxygenase-2 in rat renal thick ascending limb cells.
abstract: Cyclooxygenase-2 (COX-2) is constitutively expressed in a subset of thick ascending limb cells in the cortex and medulla and increases when the renin-angiotensin and kallikrein-kinin systems are activated. Although the contribution of angiotensin II to the regulation of COX-2 is known, the effects of bradykinin on COX-2 expression have not been determined in this nephron segment. We evaluated expression of B2 bradykinin receptors in thick ascending limb cells containing COX-2 and the effect of bradykinin on COX-2 expression in primary cultured medullary thick ascending cells. The presence of B2 receptors was studied in renal sections by immunohistochemistry with antibodies against B2, COX-2, and Tamm-Horsfall glycoprotein. B2 receptors were detected on the apical and basolateral portion of the thick ascending cells. These cells also contained COX-2, suggesting that COX-2 expression may be regulated via B2 receptor. Incubation of cultured medullary thick ascending cells with bradykinin (10(-7) to 10(-5) mol/L) induced a significant increase on COX-2 protein expression. Maximal expression of COX-2 was observed 4 hours after exposure to bradykinin (10(-7) mol/L), effect abolished by a B2 receptor antagonist (HOE-140; 10(-6) mol/L). Prostaglandin E2 production increased when these cells were challenged with bradykinin for 4 hours, indicating that COX-2 was enzymatically active. We have demonstrated (1) the presence of B2 receptors in thick ascending limb cells expressing COX-2 and (2) the stimulatory effect of bradykinin on COX-2 protein expression, via B2 receptors, in cultured medullary thick ascending cells. We suggest that bradykinin can affect ion transport in the thick ascending limb via a COX-2-mediated mechanism.
authors.affiliation: Department of Physiology, Pontificia Universidad Catolica de Chile, Santiago, Chile.
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Rodriguez
authors.forename: Carlos P
authors.initials: CP
authors.lastname: Vio
authors.forename: Paulina L
authors.initials: PL
authors.lastname: Pedraza
authors.forename: John C
authors.initials: JC
authors.lastname: McGiff
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Ferreri
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000378:metabolism* / Q000494:pharmacology; D065094:Bradykinin B2 Receptor Antagonists; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043782:Receptor, Bradykinin B2 / Q000378:metabolism
chemical_list: D065094:Bradykinin B2 Receptor Antagonists; D007527:Isoenzymes; D043782:Receptor, Bradykinin B2; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D001920:Bradykinin