Leukotriene C4 and D4 contract rat glomerular mesangial cells.
The sulfidopeptide leukotrienes, LTC4 and LTD4, have vasoconstrictor effects in the kidney, reducing both renal blood flow and the glomerular filtration rate. As one mechanism regulating the glomerular filtration rate, mesangial cell contraction may reduce the capillary surface area, thereby lowering the ultrafiltration coefficient. Using image analysis microscopy to quantify changes in cell morphology, we found that LTC4 and LTD4 (1 X 10(-12)M to 1 X 10(-6)M) reduced the cross-sectional area of cultured mesangial cells from rat glomeruli. The response to LTC4 and LTD4 (10(-6)M), as measured by the percentage of responding cells (30 to 35%), the maximum decrease in cross-sectional area (25 to 32%), and the time course was identical to that for angiotensin II (10(-6)M). The contraction induced by LTD4 was attenuated by an LTD4 receptor antagonist (4R,5S,6Z-nor-LTD1). Also, preincubation with colchicine prevented LTC4-induced contraction. Leukotriene B4, a non-sulfidopeptide leukotriene that stimulates chemotaxis and chemokinesis, had negligible agonist activity. Mesangial cells cultured on less adhesive teflon membranes were more responsive to LTD4 (62% of cells responded) than cells cultured on glass or polystyrene (35% of cells responded). Mesangial cell contraction was not merely a shape-change as a result of cell damage, since cellular injury was not documented by lactate dehydrogenase release and proliferation of mesangial cells was not retarded by LTC4. Furthermore, the contraction was independent of cell size. Because leukotrienes stimulate cyclooxygenase products in other cells, we examined the ability of the sulfidopeptide leukotrienes to stimulate prostaglandin and thromboxane synthesis. LTC4 and LTD4 did not stimulate PGE2 formation, the major cyclooxygenase product of rat mesangial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Simonson
M S
MS
Dunn
M J
MJ
D000818:Animals; D002478:Cells, Cultured; D003078:Colchicine / Q000494:pharmacology; D015232:Dinoprostone; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007091:Image Processing, Computer-Assisted / Q000379:methods; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008853:Microscopy / Q000379:methods; D011458:Prostaglandins E / Q000096:biosynthesis; D051381:Rats; D013189:SRS-A / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000096:biosynthesis
D011458:Prostaglandins E; D013189:SRS-A; D013929:Thromboxane B2; D007770:L-Lactate Dehydrogenase; D015232:Dinoprostone; D003078:Colchicine