Effects of PGE2 and a thromboxane A2 analogue on uptake of IgG complexes and LDL by mesangial cells

P. C. Singhal, S. Gupta, Z. Shen, D. Schlondorff

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Vasoactive agents such as angiotensin (ANG) and eicosanoids can influence macromolecular deposition in the glomerular mesangium. We studied whether prostaglandin E2 (PGE2) and U-46619 (a stable analogue of thromboxane A2) could directly affect the uptake of immunoglobulin G (IgG) complexes or low-density lipoprotein (LDL) by cultured rat mesangial cells (MC). Preincubation of MC with PGE2 (10-6 M) resulted in decreased uptake (in counts·min-1·well-1) of IgG complexes (PGE2, 2,589 ± 72; control, 3,840 ± 114; P < 0.001) and LDL particles (PGE2, 23,176 ± 1,145; control, 37,216 ± 4,520; P < 0.05). MC preincubated with forskolin (10-5 M) also showed decreased uptake of IgG complexes (forskolin, 2,896 ± 196; control, 3,840 ± 114; P < 0.005) and LDL particles (forskolin, 23,176 ± 1,145; control, 37,216 ± 4,520; P < 0.05). In contrast, preincubation with ANG II (5 X 10-7 M) showed significantly higher uptake of IgG complexes (ANG II, 4,475 ± 282; control, 3,787 ± 277; P < 0.05) and LDL (ANG II, 48,573 ± 1,079; control, 44,697 ± 770; P < 0.05). Similarly, preincubation with U-46619 (10-6 M) resulted in significantly higher uptake of IgG complexes (U-46619, 5,370 ± 300; control, 3,659 ± 307; P < 0.02) and LDL (U-46619, 48,298 ± 1,418; control, 44,697 ± 770; P < 0.05). After preincubation with cyclooxygenase inhibitor meclofenamate (10-6 M), ANG II (5 X 10-7 M) resulted in a significantly higher uptake of IgG complexes compared with uptake by MC treated with ANG II alone (P < 0.05). Similarly, MC preincubated with meclofenamate (10-6 M) enhanced uptake of LDL (53,328 ± 1,334, P < 0.005) in response to U-46619 compared with U-46619 alone (48,298 ± 1,418). This suggests that inhibition of PGE2 synthesis by meclofenamate enhances the effect of ANG II and U-46619 on macromolecular uptake. Because both forskolin and PGE2 activate adenylate cyclase in MC, it appears that the action of these agents on MC uptake of macromolecules may be mediated via generation of adenosine 3',5'-cyclic monophosphate.

Original languageEnglish (US)
Pages (from-to)F537-F544
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Volume261
Issue number3 30-3
DOIs
StatePublished - 1991
Externally publishedYes

Keywords

  • Actin filaments
  • Angiotensin II
  • Forskolin
  • Immunoglobulin G complexes
  • Low-density lipoprotein
  • Meclofenamate
  • N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-phallacidin
  • Prostaglandin E
  • Thromboxane A

ASJC Scopus subject areas

  • Physiology

Fingerprint Dive into the research topics of 'Effects of PGE<sub>2</sub> and a thromboxane A<sub>2</sub> analogue on uptake of IgG complexes and LDL by mesangial cells'. Together they form a unique fingerprint.

  • Cite this