The activation of phospholipase D participates in the mitogenic action of arginine vasopressin in cultured rat glomerular mesangial cells.
The present study was undertaken to determine whether phospholipase D participates in the mitogenic action of arginine vasopressin (AVP) in cultured rat glomerular mesangial cells. AVP promptly increased the phosphatidylethanol formation in a concentration-dependent manner, which indicates the activation of phospholipase D. When cells were preincubated with 2,3-diphosphoglycerate or carbobenzyloxy-leucine-tyrosine-chloromethylketone (zLYCK), inhibitors of phospholipase D, the 1 x 10(-7) M AVP-produced phosphatidylethanol was significantly attenuated. Also, inhibitors of protein kinase C, staurosporine and calphostin C, reduced the AVP-induced increase in phosphatidylethanol. AVP activated mitogen-activated protein (MAP) kinase in a concentration-dependent manner. Such an activation was significantly reduced by 2,3-diphosphoglycerate, zLYCK, or staurosporine. Also, AVP stimulated [3H]thymidine incorporation, an effect significantly less in the presence of 2,3-diphosphoglycerate or zLYCK. Similar results were obtained with exogenous bacterial phospholipase D. Both MAP kinase and [3H]thymidine incorporation were not altered by 2,3-diphosphoglycerate or zLYCK per se. These results indicate that AVP activates phospholipase D and promotes cellular growth mediated through phospholipase D, in addition to a phospholipase C-dependent signal transduction, in glomerular mesangial cells.
Kusaka
I
I
Division of Endocrinology and Metabolism, Department of Medicine, Jichi Medical School, Tochigi, Japan.
Ishikawa
S E
SE
Higashiyama
M
M
Saito
T
T
Nagasaka
S
S
Saito
T
T
D019794:2,3-Diphosphoglycerate; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002478:Cells, Cultured; D004163:Diphosphoglyceric Acids / Q000494:pharmacology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D020404:Glycerophospholipids; D008297:Male; D008934:Mitogens / Q000494:pharmacology*; D009281:Naphthalenes / Q000494:pharmacology; D010712:Phosphatidic Acids / Q000037:antagonists & inhibitors / Q000378:metabolism; D010739:Phospholipase D / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D019311:Staurosporine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004163:Diphosphoglyceric Acids; D004791:Enzyme Inhibitors; D020404:Glycerophospholipids; D008934:Mitogens; D009281:Naphthalenes; D010712:Phosphatidic Acids; C051521:phosphatidylethanol; D001127:Arginine Vasopressin; D019794:2,3-Diphosphoglycerate; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010739:Phospholipase D; D019311:Staurosporine; C058819:calphostin C; D013755:Tetradecanoylphorbol Acetate