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

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

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Vas-oactive 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 × 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 × 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)
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Volume261
Issue number3 30-3
StatePublished - 1991
Externally publishedYes

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15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Thromboxane A2
Mesangial Cells
LDL Lipoproteins
Dinoprostone
Angiotensin II
Immunoglobulin G
Meclofenamic Acid
Colforsin
Glomerular Mesangium
Cyclooxygenase Inhibitors
Eicosanoids
Angiotensins
Adenylyl Cyclases
Adenosine

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Medicine(all)

Cite this

Effects of PGE2 and a thromboxane A2 analogue on uptake of IgG complexes and LDL by mesangial cells. / Singhal, P. C.; Gupta, Sanjeev; Shen, Z.; Schlondorff, D.

In: American Journal of Physiology - Renal Fluid and Electrolyte Physiology, Vol. 261, No. 3 30-3, 1991.

Research output: Contribution to journalArticle

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T1 - Effects of PGE2 and a thromboxane A2 analogue on uptake of IgG complexes and LDL by mesangial cells

AU - Singhal, P. C.

AU - Gupta, Sanjeev

AU - Shen, Z.

AU - Schlondorff, D.

PY - 1991

Y1 - 1991

N2 - Vas-oactive 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 × 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 × 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.

AB - Vas-oactive 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 × 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 × 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.

KW - Angiotensin II; meclofenamate

KW - Forskolin; actin filaments

KW - Immunoglobulin G complexes

KW - Low-density lipoprotein

KW - N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-phallacidin

KW - Prostaglandin E

KW - Thromboxane A

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M3 - Article

VL - 261

JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

SN - 1931-857X

IS - 3 30-3

ER -