title: Interaction of adrenomedullin and platelet-derived growth factor on rat mesangial cell production of endothelin.
abstract: Adrenomedullin has recently been isolated from human pheochromocytoma. We designed the present study to examine the effect of adrenomedullin on the production of the vasoconstrictive and growth-promoting peptide endothelin-1 (ET-1) after stimulation with platelet-derived growth factor (PDGF) in cultured rat glomerular mesangial cells. PDGF stimulated ET-1 production in a concentration-dependent manner. Rat adrenomedullin inhibited this stimulated ET-1 production in a concentration-dependent manner between 10(-7) and 10(-8) mol/L. Rat adrenomedullin also increased the cellular level of cAMP in a concentration-dependent manner between 10(-7) and 10(-8) mol/L. Human adrenomedullin was less effective than rat adrenomedullin with respect to inhibiting ET-1 production and increasing cAMP levels. The addition of 8-bromo-cAMP (10(-3) and 10(-4) mol/L) reduced PDGF-induced ET-1 production. Furthermore, forskolin (10(-4) and 10(-5) mol/L), an activator of adenylate cyclase, reduced PDGF-induced ET-1 production. In contrast, the basal production of ET-1 was not significantly altered by rat and human adrenomedullin. These results indicate that adrenomedullin inhibits PDGF-induced ET-1 production in cultured rat mesangial cells, probably through a cAMP-dependent process.
authors.affiliation: First Department of Internal Medicine, Osaka City University Medical School, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kohno
authors.forename: K
authors.initials: K
authors.lastname: Yasunari
authors.forename: K
authors.initials: K
authors.lastname: Yokokawa
authors.forename: T
authors.initials: T
authors.lastname: Horio
authors.forename: M
authors.initials: M
authors.lastname: Ikeda
authors.forename: H
authors.initials: H
authors.lastname: Kano
authors.forename: M
authors.initials: M
authors.lastname: Minami
authors.forename: T
authors.initials: T
authors.lastname: Hanehira
authors.forename: J
authors.initials: J
authors.lastname: Yoskikawa
mesh_terms: D053607:Adrenomedullin; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D004347:Drug Interactions; D016232:Endothelins / Q000096:biosynthesis*; D005920:Glomerular Mesangium / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000959:Antihypertensive Agents; D016232:Endothelins; D010455:Peptides; D010982:Platelet-Derived Growth Factor; D053607:Adrenomedullin