Effect of thrombin on proliferation, contraction and prostaglandin production of rat glomerular mesangial cells in culture

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 263; no. 1; pp. 404 - 412
• Main Authors: ALBRIGHTSON, C. R, NAMBI, P, ZABKO-POTAPOVICH, B, DYTKO, G, GROOM, T
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Pharmacology and Experimental Therapeutics 01.10.1992
• Subjects: Animals; Biological and medical sciences; Calcium - metabolism; Cell Division - drug effects; Cells, Cultured; Fundamental and applied biological sciences. Psychology; Glomerular Mesangium - drug effects; Glomerular Mesangium - metabolism; Glomerular Mesangium - ultrastructure; Hirudins - pharmacology; Indomethacin - pharmacology; Prostaglandins E - biosynthesis; Rats; Rats, Sprague-Dawley; Thrombin - pharmacology; Thymidine - metabolism; Vertebrates: urinary system; Cell proliferation; Cell culture; Calcium; Prostaglandin; Rat; Enzyme; Mesangial cell; Rodentia; Contractility; Thrombin; Metabolism; Kidney; Renal glomerulus; Vertebrata; Mammalia; Urinary system; Mitogen
• ISSN: 0022-3565; 1521-0103

The effect of thrombin on mesangial cell function was investigated. Thrombin caused a dose-dependent increase in [3H] thymidine incorporation (EC50 = 0.36 +/- 0.09 U/ml), intracellular calcium [(Ca++)i] mobilization (EC50 = 1.9 +/- 0.5 U/ml) and prostaglandin E2 (PGE2) production (EC50 = 0.25 +/- 0.02 U/ml) in rat glomerular mesangial cells. These effects were blocked by the thrombin inhibitor, hirudin (KB = 10.4 +/- 0.2 nM). The role of (Ca++)i mobilization and arachidonate metabolism in thrombin-stimulated proliferation was tested by the addition of the calcium channel blocker, nifedipine, and the cyclooxygenase inhibitor, indomethacin, to mesangial cell cultures. Indomethacin, at doses that completely inhibited the thrombin-mediated production of PGE2, had no significant effect on proliferation. The Ca++ channel blocker, nifedipine, inhibited both PGE2 production and [3H] thymidine incorporation in a dose-dependent fashion, but only at concentrations considered nonspecific. In addition to its effects on PGE2, thymidine incorporation and Ca++ mobilization, thrombin caused mesangial cell contraction as determined by a substrate distortion technique. This effect was not inhibited by indomethacin. These results indicate that thrombin can alter mesangial cell function in vitro.