title: Effects of PGE2 and a thromboxane A2 analogue on uptake of IgG complexes and LDL by mesangial cells.
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 less than 0.001) and LDL particles (PGE2, 23,176 +/- 1,145; control, 37,216 +/- 4,520; P less than 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 less than 0.005) and LDL particles (forskolin, 23,176 +/- 1,145; control, 37,216 +/- 4,520; P less than 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 less than 0.05) and LDL (ANG II, 48,573 +/- 1,079; control, 44,697 +/- 770; P less than 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 less than 0.02) and LDL (U-46619, 48,298 +/- 1,418; control, 44,697 +/- 770; P less than 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 less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, Long Island Jewish Medical Center, New Hyde Park, New York 11042.
authors.forename: P C
authors.initials: PC
authors.lastname: Singhal
authors.forename: S
authors.initials: S
authors.lastname: Gupta
authors.forename: Z
authors.initials: Z
authors.lastname: Shen
authors.forename: D
authors.initials: D
authors.lastname: Schlondorff
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000199:Actins / Q000032:analysis; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005920:Glomerular Mesangium / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000378:metabolism*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D051381:Rats; D013928:Thromboxane A2 / Q000031:analogs & derivatives
chemical_list: D000199:Actins; D007074:Immunoglobulin G; D008077:Lipoproteins, LDL; D011450:Prostaglandin Endoperoxides, Synthetic; D005576:Colforsin; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015232:Dinoprostone; D015056:1-Methyl-3-isobutylxanthine