Endothelin Type B Receptor–Induced Sustained Ca2+ Influx Involves Gq/11/Phospholipase C–Independent, p38 Mitogen-Activated Protein Kinase–Dependent Activation of Na+/H+ Exchanger

Tsunaki Higa; Takahiro Horinouchi; Hiroyuki Aoyagi; Hiroshi Asano; Tadashi Nishiya; Arata Nishimoto; Ikunobu Muramatsu; Soichi Miwa

doi:10.1254/jphs.10102SC

Short Communications

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

Tsunaki Higa, Takahiro Horinouchi, Hiroyuki Aoyagi, Hiroshi Asano, Tadashi Nishiya, Arata Nishimoto, Ikunobu Muramatsu, Soichi Miwa

Author information

Tsunaki Higa
Department of Cellular Pharmacology, Hokkaido University Graduate School of Medicine, Japan
Takahiro Horinouchi
Department of Cellular Pharmacology, Hokkaido University Graduate School of Medicine, Japan
Hiroyuki Aoyagi
Department of Cellular Pharmacology, Hokkaido University Graduate School of Medicine, Japan
Hiroshi Asano
Department of Cellular Pharmacology, Hokkaido University Graduate School of Medicine, Japan
Tadashi Nishiya
Department of Cellular Pharmacology, Hokkaido University Graduate School of Medicine, Japan
Arata Nishimoto
Department of Cellular Pharmacology, Hokkaido University Graduate School of Medicine, Japan
Ikunobu Muramatsu
Division of Pharmacology, Department of Biochemistry and Bioinformative Sciences, School of Medicine, University of Fukui, Japan
Soichi Miwa
Department of Cellular Pharmacology, Hokkaido University Graduate School of Medicine, Japan

Keywords: endothelin type B receptor, Na⁺/H⁺ exchanger, p38 mitogen-activated protein kinase

JOURNAL FREE ACCESS

2010 Volume 113 Issue 3 Pages 276-280

DOI https://doi.org/10.1254/jphs.10102SC

View "Advance Publication" version (June 29, 2010).

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Abstract

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_BR) and endogenous P2Y receptor (P2Y-R), endothelin-1 elicited a sustained Ca²⁺ influx depending on G_q/11protein, 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_BR 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_BR- mediated sustained Ca²⁺ influx.

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