title: Regulation of cyclooxygenase expression by vasopressin in rat renal medulla.
abstract: The antagonism between prostaglandin and vasopressin represents a classic negative feedback loop. It is not clear whether cyclooxygenase (COX)-2 and/or COX-1 expression is involved in elevated prostaglandin production stimulated by vasopressin in vivo. In the present study, we explored vasopressin regulation of medullary COX-2 and COX-1 expression acutely and chronically in rats. Medullary COX-1 expression was moderately lower and COX-2 expression was significantly lower in adult male Brattleboro rats than age-matched Long-Evans controls. Chronic treatment of Brattleboro rats with vasopressin for 1 wk led to a decrease in urine volume and a moderate increase in medullary COX-1; in contrast, medullary COX-2 expression was almost undetectable in untreated rats but was dramatically up-regulated with vasopressin treatment and was accompanied by increased urinary prostaglandin E(2) excretion. Further investigation revealed that both V1 and V2 receptors were involved in chronic medullary COX-1 and COX-2 up-regulation. Acute treatment with specific V1 or V2 receptor agonists resulted in specific increases in medullary COX-2, which was prevented by furosemide. Vasopressin did not affect COX-2 expression in cultured renomedullary interstitial cells. These data demonstrate that vasopressin stimulates medullary COX-2 expression through activation of both V1 and V2 receptors, and this stimulation is indirect and probably involves increased medullary electrolyte tonicity.
authors.affiliation: George O'Bien Center for Kidney and Urologic Diseases, and Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
authors.forename: Ming-Zhi
authors.initials: MZ
authors.lastname: Zhang
authors.forename: Pedro
authors.initials: P
authors.lastname: Sanchez Lopez
authors.forename: James A
authors.initials: JA
authors.lastname: McKanna
authors.forename: Raymond C
authors.initials: RC
authors.lastname: Harris
mesh_terms: D000818:Animals; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000652:urine; D015536:Down-Regulation / Q000187:drug effects; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism*; D007679:Kidney Medulla / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008565:Membrane Proteins; D009994:Osmolar Concentration; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D011910:Rats, Brattleboro; D020318:Rats, Long-Evans; D017483:Receptors, Vasopressin / Q000819:agonists / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D014667:Vasopressins / Q000494:pharmacology*
chemical_list: D007527:Isoenzymes; D008565:Membrane Proteins; D017483:Receptors, Vasopressin; D014667:Vasopressins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D015232:Dinoprostone