Effect of hypothalamic-hypophysary inhibitory factor on mesangial cell activation.
We examined the effect of a sodium pump inhibitor isolated from bovine hypothalamus and pituitary tissues on contraction, proliferation, and calcium mobilization in primary cultures of rat mesangial cells. Hypothalamic-hypophysary inhibitory factor (HHIF) inhibited rubidium uptake in a concentration-dependent manner (0.2 U/mL: 56.8 +/- 6.3% inhibition). It also induced a concentration- and time-dependent decrease in planar cell surface area. Maximal contraction (25 +/- 5% reduction in cell size) was reached at 60 minutes with a concentration of 0.2 U/mL. This effect was inhibited by both verapamil and TMB-8 (10(-5) mol/L). HHIF was also observed to increase DNA synthesis (0.2 U/mL: 4361 +/- 168 versus 2129 +/- 162 cpm per well under control conditions) and cell proliferation (0.2 U/mL: 52,290 +/- 1931 versus 10,512 +/- 121 cells per well under control conditions). Both effects were also inhibited by verapamil and TMB-8. Moreover, HHIF induced the expression of immediate early genes c-fos and c-jun mRNA. HHIF-induced effects were accompanied by an increase in cytosolic free calcium (203 +/- 58 versus 101 +/- 2 nmol/L under control conditions), which was inhibited by verapamil and TMB-8. In summary, HHIF induces mesangial cell contraction and proliferation; these effects seem to be mediated by an increase in cytosolic free calcium levels.
D000704:Analysis of Variance; D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002417:Cattle; D002455:Cell Division; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004587:Electrophoresis, Agar Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D015870:Gene Expression; D016762:Genes, fos; D016758:Genes, jun; D005920:Glomerular Mesangium / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008969:Molecular Sequence Data; D010042:Ouabain / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D013499:Surface Properties; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; C083016:sodium-potassium ATPase inhibitory factor; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D010042:Ouabain; D005707:Gallic Acid; D004247:DNA; D014700:Verapamil; D002118:Calcium