Cannabinoid receptor CB1 activates the Na+/H+ exchanger NHE‐1 isoform via Gi‐mediated mitogen activated protein kinase signaling transduction pathways

FEBS Letters

Pouyssegur, J.¹  Bouaboula, M.²  Casellas, P.²  Bianchini, L.¹  McKenzie, F.R.¹ 

[1] UMR CNRS 6543, Centre de Biochimie, Faculté des Sciences, Parc Valrose, F-06108 Nice Cedex 2, France;Sanofi Recherche, Ligne Immunologie, 371 rue du Prof. Joseph Blayac, F-34184 Montpellier Cedex 4, France

关键词: Cannabinoid receptor 1;    SR 141716A;    Inverse agonist;    Na+/H+ exchanger NHE-1 isoform;    Mitogen-activated protein kinase;    CB1;    cannabinoid receptor 1;    NHE-1;    Na+/H+ exchanger NHE-1 isoform;    MAPK;    mitogen-activated protein kinase;    CHO;    Chinese hamster ovary cells;    RTK;    receptor tyrosine kinase;    GPCR;    G-protein-coupled receptor;   

DOI  :  10.1016/S0014-5793(99)00395-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

We previously showed that the cannabinoid receptor CB1 stably transfected in Chinese hamster ovary cells was constitutively active and could be inhibited by the inverse agonist SR 141716A. In the present study, we demonstrate that the cannabinoid agonist CP-55940 induced cytosol alkalinization of CHO-CB1 cells in a dose- and time-dependent manner via activation of the Na⁺/H⁺ exchanger NHE-1 isoform. By contrast, the inverse agonist SR 141716A induced acidification of the cell cytosol, suggesting that the Na⁺/H⁺ exchanger NHE-1 was constitutively activated by the CB1 receptor. CB1-mediated NHE1 activation was prevented by both pertussis toxin treatment and the specific MAP kinase inhibitor PD98059. NHE-1 and p42/p44 MAPK had a similar time course of activation in response to the addition of CP-55940 to CHO-CB1 cells. These results suggest that CB1 stimulates NHE-1 by G_i/o-mediated activation of p42/p44 MAP kinase and highlight a cellular physiological process targeted by CB1.

【 授权许可】

Unknown