Physiol. Res. 55: 535-542, 2006

Hypoxic Stress-Enhanced Expression and Release of Adrenomedullin (AM) and Up-Regulated AM Receptors, while Glucose Starvation Reduced AM Expression and Release and Down-Regulated AM Receptors in Monkey Renal Cells


1Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava, 2Department of Information Technology, Slovak Gas Industry, Bratislava, 3Faculty of Material Science and Technology, Slovak University of Technology, Bratislava, Slovak Republic

Received date August 4, 2005
Accepted date November 21, 2005
On-line available December 12, 2005

The proliferative peptide adrenomedullin (AM) has a wide distribution in a variety of tissues and cells. The mechanism how the AM gene is regulated in cells is not yet known. The renal cortex, renal vascular smooth muscles, glomeruli and tubular epithelial cells are very sensitive to hypoxia. Renal hypoxia produces acute renal tubular necrosis and markedly induces AM expression in damaged cells. However, little information is available regarding the possible pathophysiological production and release of renal tubular AM. Regulation of membrane-bound AM receptors in renal cells has not yet been systematically studied. To elucidate the potential pathological role of human AM we examined the production and release of AM, as well as the characteristics of surface membrane AM receptors in cultured monkey renal tubular epithelial cells (RC) exposed to hypoxia, induced with endothelin-1, and subjected to glucose deprivation. Exposure of RC to hypoxia (1 % O2, 5 % CO2 in N2), and to phorbol 12-myristate 13-acetate (PMA) increased production and secretion of AM and increased specific [125I]AM binding on RC. Metabolic stress (1 % glucose in the cultivation medium) and preincubation of RC with rival peptide endothelin-1 significantly reduced immunoreactive-AM in a conditioned medium and whole cell surface membrane AM binding on RC. Altogether, our data suggest that the AM is involved in the adaptation of renal tubular cells to hypoxia. Increased expression of AM mRNA and regulation of AM receptors in metabolic stress may function as an important autocrine/paracrine regulator(s) of renal tubular epithelial cells.

Key words
Adrenomedullin expression and release • Ligand binding studies • Renal tubular epithelial cells • Radioimmunoassays • Hypoxia • Glucose repression

© 2006 by the Institute of Physiology, Czech Academy of Sciences