Cyclosporine promotes glomerular endothelin binding in Vivo

Midori Awazu, Masanori Sugiura, Tadashi Inagami, Lekuni Ichikawa, Valentina Kon

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29 Citations (Scopus)

Abstract

It has previously been shown that administration of cyclosporine causes a prompt (within 15 min after infusion) increase in circulating level of endothelin 1 and a pattern of glomerular hypoperfusion and hypofiltration which can be ameliorated with antiendothelin antibody. We now show that 60 min after cyclosporine, serum endothelin 1 level falls to <2.55 ± 0.31 pg/mL (N = 6), a value comparable to that found in normal animals (<2 pg/mL). The study presented here also examines whether sustained cyclosporine-induced glomerular dysfunction is associated with altered endothelin receptor characteristics. Saturation and competitive inhibition binding studies in isolated glomerular membranes showed two binding sites. Of these, the density of the low-affinity site was affected by cyclosporine treatment (851 ± 117 versus 425 ± 61 fmol/mg of protein; P< 0.05; N= 6) without a change in equilibrium dissociation constant, KD. The high-affinity site was not affected. The receptor characteristics of another vasoconstrictor, angiotensin II, were not affected by cyclosporine. In addition, there was no difference in endothelin binding sites in hepatic tissue between cyclosporine and control rats. These results raise the intriguing possibility that cyclosporine-induced glomerular dysfunction involves upregulation of endothelin binding sites and that altered endothelin receptors appear specific to the kidney.

Original languageEnglish
Pages (from-to)1253-1258
Number of pages6
JournalJournal of the American Society of Nephrology
Volume1
Issue number11
Publication statusPublished - 1991 May

Keywords

  • Angiotensin
  • Cyclosporine
  • Endothelin receptor
  • Kidney

ASJC Scopus subject areas

  • Nephrology

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    Awazu, M., Sugiura, M., Inagami, T., Ichikawa, L., & Kon, V. (1991). Cyclosporine promotes glomerular endothelin binding in Vivo. Journal of the American Society of Nephrology, 1(11), 1253-1258.