SECRETION OF ADRENOMEDULLIN BY RENAL TUBULAR CELL-LINES

Adrenomedullin (AM) is a novel and potent vasodilator peptide original ly isolated from human pheochromocytoma. The present study was designe d to study whether AM is produced by and secreted from renal tubular c ell lines and whether arginine vasopressin (AVP) affects AM secretion from these cell lines. Three renal tubular cell lines derived from dif ferent species (LLCPK1, MDCK, and MDBK) secrete AM-like immunoreactivi ty (AM-LI) into culture medium, the immunological and physicochemical properties of which are similar to that of synthetic human AM as evalu ated by reverse-phase highperformance liquid chromatography. Among the three cell lines, AVP in combination with a phosphodiesterase inhibit or (isobutylmethylxanthine) stimulated AM-LI secretion most potently f rom MDCK cells in a time-and dose-dependent manner. In MDCK cells, a V -2 receptor agonist (deamino-D-Arg(8)-vasopressin) dose-dependently st imulated AM-LI secretion in the same manner as AVP. Furthermore, the A VP-induced AM-LI secretion was blocked by a V-2 receptor antagonist (O PC31260), but not by a V-1 receptor antagonist (OPC21268). These data indicate that AM is secreted from renal tubular cell lines and that AV P stimulates AM secretion via V-2 receptors, suggesting its autocrine/ paracrine role in renal function.