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)