TY - JOUR
T1 - Mechanism of induction of prostaglandin E2 production by endothelin 1 in cultured rat mesangial cells
AU - Fukunaga, Megumu
AU - Fujiwara, Yoshihiro
AU - Ochi, Satoshi
AU - Yokoyama, Kenji
AU - Shoji, Tatsuya
AU - Fukuhara, Yoshifumi
AU - Orita, Yoshimasa
AU - Kamada, Takenobu
AU - Badr, Kamal F.
AU - Ueda, Naohiko
PY - 1996/11
Y1 - 1996/11
N2 - The phospholipase A2 inhibitors mepacrine, ONO-RS-082, and AACOCF3 completely inhibited prostaglandin E2 production induced by endothelin 1 in cultured rat mesangial cells, suggesting that phospholipase A2 is a critical enzyme in this process. TMB-8, an inhibitor of calcium mobilization from intracellular stores, abolished its production, while neither nicardipine nor chelation of extracellular calcium by EGTA did. The protein kinase C inhibitors, H-7 and staurosporine, and downregulation of protein kinase C could not inhibit prostaglandin E2 production, while W-7, a calmodulin inhibitor, abolished it. Pertussis toxin never influenced its production. Thus, endothelin 1 evokes prostaglandin E2 production in mesangial cells mainly through the activation of phospholipase A2, dependent on intracellular calcium and calmodulin and independent of extracellular calcium, protein kinase C, and pertussis toxin sensitive guanosine 5'-triphosphate binding proteins.
AB - The phospholipase A2 inhibitors mepacrine, ONO-RS-082, and AACOCF3 completely inhibited prostaglandin E2 production induced by endothelin 1 in cultured rat mesangial cells, suggesting that phospholipase A2 is a critical enzyme in this process. TMB-8, an inhibitor of calcium mobilization from intracellular stores, abolished its production, while neither nicardipine nor chelation of extracellular calcium by EGTA did. The protein kinase C inhibitors, H-7 and staurosporine, and downregulation of protein kinase C could not inhibit prostaglandin E2 production, while W-7, a calmodulin inhibitor, abolished it. Pertussis toxin never influenced its production. Thus, endothelin 1 evokes prostaglandin E2 production in mesangial cells mainly through the activation of phospholipase A2, dependent on intracellular calcium and calmodulin and independent of extracellular calcium, protein kinase C, and pertussis toxin sensitive guanosine 5'-triphosphate binding proteins.
KW - Calmodulin
KW - Endothelin 1
KW - Guanosine 5'-triphosphate binding proteins
KW - Intracellular calcium
KW - Mesangial cells
KW - Phospholipase A
KW - Protein kinase C
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M3 - Article
C2 - 9001889
AN - SCOPUS:16144363328
SN - 1018-7782
VL - 4
SP - 340
EP - 349
JO - Experimental Nephrology
JF - Experimental Nephrology
IS - 6
ER -