Endothelin type B receptor-induced sustained Ca2+ influx involves G(q/11)/phospholipase C-independent, p38 mitogen-activated protein kinase-dependent activation of Na+/H+ exchanger.
The mechanism for sustained Ca2+ influx activated by G protein-coupled receptors was examined. In Chinese hamster ovary cells expressing recombinant human endothelin type B receptor (ET(B)R) and endogenous P2Y receptor (P2Y-R), endothelin-1 elicited a sustained Ca2+ influx depending on G(q/11 )protein, phospholipase C (PLC), Na+/H+ exchanger (NHE), and p38 mitogen-activated protein kinase (p38MAPK), whereas P2Y-R-induced sustained Ca2+ influx was negligible. Functional studies showed that NHE activation by ET(B)R was mediated via p38MAPK but not G(q/11)/PLC, while that by P2Y-R involves only G(q/11)/PLC/p38MAPK. These results suggest that G(q/11)/PLC-independent NHE activation via p38MAPK plays an important role in ET(B)R- mediated sustained Ca2+ influx.
Higa
Tsunaki
T
Department of Cellular Pharmacology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Horinouchi
Takahiro
T
Aoyagi
Hiroyuki
H
Asano
Hiroshi
H
Nishiya
Tadashi
T
Nishimoto
Arata
A
Muramatsu
Ikunobu
I
Miwa
Soichi
S
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D020013:Calcium Signaling; D006224:Cricetinae; D003412:Cricetulus; D019332:Endothelin-1 / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D009994:Osmolar Concentration; D010766:Phosphorylation; D058910:Purinergic P2 Receptor Agonists; D044023:Receptor, Endothelin B / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013997:Time Factors; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D019332:Endothelin-1; D004791:Enzyme Inhibitors; D058910:Purinergic P2 Receptor Agonists; D044023:Receptor, Endothelin B; D018048:Receptors, Purinergic P2; D017923:Sodium-Hydrogen Exchangers; D000255:Adenosine Triphosphate; D048051:p38 Mitogen-Activated Protein Kinases; D010738:Type C Phospholipases; D043802:GTP-Binding Protein alpha Subunits, Gq-G11