Comparison of the effect of rapamycin and FK506 on release of prostacyclin and endothelin in vitro

Randall W. Yatscoff; Jon Fryer; James A. Thliveris

doi:10.1016/0009-9120(93)90118-P

Comparison of the effect of rapamycin and FK506 on release of prostacyclin and endothelin in vitro

Randall W. Yatscoff^*, Jon Fryer, James A. Thliveris

^*Corresponding author for this work

Surgery, Transplant Surgery Division

Research output: Contribution to journal › Article › peer-review

43 Scopus citations

Abstract

Alterations in mesangial and endothelial cell production of vasoactive substances may be a contributing factor to the decreased renal blood flow and glomerular thrombosis associated with FK506 nephrotoxicity. In preliminary studies Rapamycin (RAPA) appears to induce fewer renal side-effects than FK506, although further documentation is required. In this study, the effects of FK506 and RAPA on release of prostacyclin, a vasodilator, and endothelin, a vasoconstrictor, were investigated in cultured rabbit mesangial and endothelial cells. In general, the effects of both RAPA and FK506 on the basal or stimulated release of prostacyclin (as measured by release of its stable metabolite, 6-keto-PGF_1α) or endothelin from mesangial cells and endothelial cells were similar with the following exceptions: RAPA resulted in a significant (p < 0.05) increase in the release of prostacyclin (PGI₂) from the endothelial cells, while in contrast, FK506 resulted in a significant decrease in the release of this analyte from these cells. The similar effects both drugs have on release of vasodilatory and vasoconstrictor substances in vitro does not explain the differences in renal side-effects of the drugs in vivo.

Original language	English (US)
Pages (from-to)	409-414
Number of pages	6
Journal	Clinical Biochemistry
Volume	26
Issue number	5
DOIs	https://doi.org/10.1016/0009-9120(93)90118-P
State	Published - Oct 1993

Funding

Company Osaka, Japan. Rapamycin was obtained as a gift from Wyeth-Ayerst Inc, Princeton, NJ, USA. We would like to thank Dr. Peter Caldwell, Department of Medicine, Columbia University, Columbia, MO, USA, for providing the angiotensin-convertinge nzyme antibody. We would also like to thank Patricia Chackowsky and Cynthia Faraci for excellent technical assistance. This work was supported by a grant from the Kidney Foundation of Canada.

Keywords

FK506
endothelin
prostacyclin
rapamycin

ASJC Scopus subject areas

Clinical Biochemistry

Access to Document

10.1016/0009-9120(93)90118-P

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title = "Comparison of the effect of rapamycin and FK506 on release of prostacyclin and endothelin in vitro",

abstract = "Alterations in mesangial and endothelial cell production of vasoactive substances may be a contributing factor to the decreased renal blood flow and glomerular thrombosis associated with FK506 nephrotoxicity. In preliminary studies Rapamycin (RAPA) appears to induce fewer renal side-effects than FK506, although further documentation is required. In this study, the effects of FK506 and RAPA on release of prostacyclin, a vasodilator, and endothelin, a vasoconstrictor, were investigated in cultured rabbit mesangial and endothelial cells. In general, the effects of both RAPA and FK506 on the basal or stimulated release of prostacyclin (as measured by release of its stable metabolite, 6-keto-PGF1α) or endothelin from mesangial cells and endothelial cells were similar with the following exceptions: RAPA resulted in a significant (p < 0.05) increase in the release of prostacyclin (PGI2) from the endothelial cells, while in contrast, FK506 resulted in a significant decrease in the release of this analyte from these cells. The similar effects both drugs have on release of vasodilatory and vasoconstrictor substances in vitro does not explain the differences in renal side-effects of the drugs in vivo.",

keywords = "FK506, endothelin, prostacyclin, rapamycin",

author = "Yatscoff, \{Randall W.\} and Jon Fryer and Thliveris, \{James A.\}",

note = "Funding Information: Company Osaka, Japan. Rapamycin was obtained as a gift from Wyeth-Ayerst Inc, Princeton, NJ, USA. We would like to thank Dr. Peter Caldwell, Department of Medicine, Columbia University, Columbia, MO, USA, for providing the angiotensin-convertinge nzyme antibody. We would also like to thank Patricia Chackowsky and Cynthia Faraci for excellent technical assistance. This work was supported by a grant from the Kidney Foundation of Canada. Copyright: Copyright 2014 Elsevier B.V., All rights reserved.",

year = "1993",

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doi = "10.1016/0009-9120(93)90118-P",

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AU - Yatscoff, Randall W.

AU - Fryer, Jon

AU - Thliveris, James A.

N1 - Funding Information: Company Osaka, Japan. Rapamycin was obtained as a gift from Wyeth-Ayerst Inc, Princeton, NJ, USA. We would like to thank Dr. Peter Caldwell, Department of Medicine, Columbia University, Columbia, MO, USA, for providing the angiotensin-convertinge nzyme antibody. We would also like to thank Patricia Chackowsky and Cynthia Faraci for excellent technical assistance. This work was supported by a grant from the Kidney Foundation of Canada. Copyright: Copyright 2014 Elsevier B.V., All rights reserved.

PY - 1993/10

Y1 - 1993/10

N2 - Alterations in mesangial and endothelial cell production of vasoactive substances may be a contributing factor to the decreased renal blood flow and glomerular thrombosis associated with FK506 nephrotoxicity. In preliminary studies Rapamycin (RAPA) appears to induce fewer renal side-effects than FK506, although further documentation is required. In this study, the effects of FK506 and RAPA on release of prostacyclin, a vasodilator, and endothelin, a vasoconstrictor, were investigated in cultured rabbit mesangial and endothelial cells. In general, the effects of both RAPA and FK506 on the basal or stimulated release of prostacyclin (as measured by release of its stable metabolite, 6-keto-PGF1α) or endothelin from mesangial cells and endothelial cells were similar with the following exceptions: RAPA resulted in a significant (p < 0.05) increase in the release of prostacyclin (PGI2) from the endothelial cells, while in contrast, FK506 resulted in a significant decrease in the release of this analyte from these cells. The similar effects both drugs have on release of vasodilatory and vasoconstrictor substances in vitro does not explain the differences in renal side-effects of the drugs in vivo.

AB - Alterations in mesangial and endothelial cell production of vasoactive substances may be a contributing factor to the decreased renal blood flow and glomerular thrombosis associated with FK506 nephrotoxicity. In preliminary studies Rapamycin (RAPA) appears to induce fewer renal side-effects than FK506, although further documentation is required. In this study, the effects of FK506 and RAPA on release of prostacyclin, a vasodilator, and endothelin, a vasoconstrictor, were investigated in cultured rabbit mesangial and endothelial cells. In general, the effects of both RAPA and FK506 on the basal or stimulated release of prostacyclin (as measured by release of its stable metabolite, 6-keto-PGF1α) or endothelin from mesangial cells and endothelial cells were similar with the following exceptions: RAPA resulted in a significant (p < 0.05) increase in the release of prostacyclin (PGI2) from the endothelial cells, while in contrast, FK506 resulted in a significant decrease in the release of this analyte from these cells. The similar effects both drugs have on release of vasodilatory and vasoconstrictor substances in vitro does not explain the differences in renal side-effects of the drugs in vivo.

KW - FK506

KW - endothelin

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Comparison of the effect of rapamycin and FK506 on release of prostacyclin and endothelin in vitro

Abstract

Funding

Keywords

ASJC Scopus subject areas

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