Cyclosporin A inhibits prostaglandin E2 formation by rat mesangial cells in culture

Journal Article · Mon May 01 00:00:00 EDT 1989 · Kidney International; (USA)

DOI:https://doi.org/10.1038/ki.1989.105· OSTI ID:5364536

Stahl, R A; Adler, S; Baker, P J; Johnson, R J; Chen, Y P; Pritzl, P; Couser, W G ^[1]

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1. Univ. of Washington, Seattle (USA)

A reversible reduction in glomerular filtration rate (GFR) is a frequent side effect in patients treated with the immunosuppressant cyclosporin A (CsA). The pathophysiology of acute CsA nephrotoxicity, however, is unclear. Since eicosanoids are local mediators of glomerular hemodynamics, they might be involved in CsA induced changes in GFR. We therefore studied the effect of CsA on prostaglandin E2 (PGE2) production by rat mesangial cells in culture. PGE2 production by mesangial cells following stimulation with angiotensin II (AII) (10(-6) M) or the Ca2+-ionophore A23187 (1 microgram/ml) was significantly inhibited when cells were grown for 24 hours in media which contained CsA (800 to 3200 ng/ml). CsA did not affect viability of mesangial cells as determined by 51Cr release or by cell proliferation measured by 3H-thymidine incorporation. CsA (3200 ng/ml) did not inhibit PGE2 formation by rat MC microsomes incubated with arachidonic acid. However, CsA, in a dose dependent manner, inhibited A23187 and angiotensin II induced release of 3H-labelled arachidonic acid from rat mesangial cells. These data demonstrate that CsA reduces PGE2 formation by rat mesangial cells in culture, probably by inhibiting the release of substrate arachidonic acid from cell membranes rather than by inhibition of cyclooxygenase. This effect may contribute to the reduction in GFR which accompanies CsA therapy.

• OSTI ID: 5364536
• Journal Information: Kidney International; (USA), Journal Name: Kidney International; (USA) Vol. 35:5; ISSN KDYIA; ISSN 0085-2538
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANGIOTENSIN
ANIMAL CELLS
ANIMALS
ARACHIDONIC ACID
AZINES
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOSYNTHESIS
BODY
CARBOXYLIC ACIDS
CARDIOVASCULAR AGENTS
CELL CONSTITUENTS
CELL CULTURES
CELL MEMBRANES
CELL PROLIFERATION
CHROMIUM 51
CHROMIUM ISOTOPES
DNA
DNA REPLICATION
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
EVEN-ODD NUCLEI
GLOBULINS
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
IMMUNOSUPPRESSIVE DRUGS
INHIBITION
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
KIDNEYS
KINETICS
MAMMALS
MEMBRANES
MICROSOMES
MONOCARBOXYLIC ACIDS
NUCLEI
NUCLEIC ACID REPLICATION
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANOIDS
ORGANS
PROSTAGLANDINS
PROTEINS
PYRIMIDINES
RADIOISOTOPES
RATS
REACTION KINETICS
RIBOSIDES
RIBOSOMES
RODENTS
SECRETION
SYNTHESIS
THYMIDINE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VASOCONSTRICTORS
VERTEBRATES