This Article Order Full text via Infotrieve Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Takeda, M. Articles by Kon, V. Search for Related Content PubMed PubMed Citation Articles by Takeda, M. Articles by Kon, V.

American Journal of Pathology, Vol 144, 473-479, Copyright © 1994 by American Society for Investigative Pathology

REGULAR ARTICLES

Divergent expression of EtA and EtB receptors in response to cyclosporine in mesangial cells

M Takeda, S Iwasaki, SE Hellings, H Yoshida, T Homma and V Kon
Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee.

We examined the effects of cyclosporine (Cy) on preproendothelin-1 (prepro Et-1) and both Et receptors, A-type (EtA) and B-type (EtB), in rat glomerular mesangial cells. Cy at 10(-5) mol/L, the concentration relevant to tissue levels in vivo, increased mRNA for prepro Et-1 after both 1 and 3 hours to 183 +/- 14% (n = 8) and 147 +/- 12% (n = 9) of levels seen in control cells. A similar pattern was observed at a lower dose of Cy (10(-6) mol/L, the concentration relevant to plasma levels in vivo): at 1 hour, expression increased to 146 +/- 15% (n = 5); at 3 hours, expression was 159 +/- 25% (n = 8). Concomitant with these changes in expression of prepro Et-1 mRNA, the Et-1 protein nearly doubled at 3 hours. Both EtA and EtB mRNA were expressed in unstimulated mesangial cells and were affected differently by Cy. Little change was observed in the EtA mRNA. In contrast, EtB mRNA increased with Cy (10(-5) mol/L) up to 129 +/- 8% (n = 6) at 1 hour and 265 +/- 62% (n = 3) at 3 hours. A similar effect was seen with the lower dose of Cy: EtB expression increased to 129 +/- 9% (n = 6) of control value at 1 hour and 253 +/- 74% (n = 4) at 3 hours. These results indicate that Cy enhances expression of mRNA for prepro Et-1 and production of mature Et-1 by glomerular mesangial cells. Further, Cy has differential effects on EtA and EtB, affecting EtA minimally while markedly increasing the expression of EtB. These results constitute the first demonstration that Et receptor subtypes are modulated in a pathophysiological setting. The divergent modulation of EtA and EtB raises the possibility that there are differences in contribution of each of the receptor subtypes to pathophysiological mechanisms of Cy toxicity.

This article has been cited by other articles:

				A. Sorokin and D. E. Kohan Physiology and pathology of endothelin-1 in renal mesangium Am J Physiol Renal Physiol, October 1, 2003; 285(4): F579 - F589. [Abstract] [Full Text] [PDF]

				Y. Abe, K. Nakayama, A. Yamanaka, T. Sakurai, and K. Goto Subtype-specific Trafficking of Endothelin Receptors J. Biol. Chem., March 17, 2000; 275(12): 8664 - 8671. [Abstract] [Full Text] [PDF]

				Y. Takeda, I. Miyamori, P. Wu, T. Yoneda, K. Furukawa, and R. Takeda Effects of an Endothelin Receptor Antagonist in Rats With Cyclosporine-Induced Hypertension Hypertension, December 1, 1995; 26(6): 932 - 936. [Abstract] [Full Text]

				S. Iwasaki, T. Homma, Y. Matsuda, and V. Kon Endothelin Receptor Subtype B Mediates Autoinduction of Endothelin-1 in Rat Mesangial Cells J. Biol. Chem., March 24, 1995; 270(12): 6997 - 7003. [Abstract] [Full Text] [PDF]