G Protein Regulation of the Na/H Antiporter in Xenopus laevis Oocytes

• Published in: The Journal of biological chemistry 1995-07, Vol.270 (30), p.17898-17901
• Main Authors: Busch, Stefan, Wieland, Thomas, Esche, Helmut, Jakobs, Karl H., Siffert, Winfried
• Format: Article
• Language: English
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.270.30.17898

We have characterized the regulation of the endogenous Na /H exchanger in Xenopus laevis oocytes by G proteins and protein kinases by measuring the ethylisopropylamiloride-sensitive Li uptake. Injection of oocytes with the stable GTP analog GTP S stimulated Li uptake up to almost 4-fold, an effect blocked by coinjection with the GDP analog, guanyl-5′-yl thiophosphate. Injection into oocytes of β subunits of the heterotrimeric G protein transducin enhanced Li uptake by about 3-fold. This stimulation was blocked by transducin α subunits, which by themselves did not influence Li uptake. Using various activators and inhibitors of protein kinases, it is demonstrated that the X. laevis oocyte Na /H antiporter can be stimulated by activation of both protein kinase A and C. Stimulation of Na /H exchanger activity by GTP S but not that induced by transducin β subunits was blocked by the protein kinase A inhibitor H-89. On the other hand, transducin β subunit-stimulated activity was prevented by the protein kinase C inhibitor, calphostin C. The non-selective protein kinase inhibitor H-7 blocked both GTP S- and transducin β subunit-stimulated Na /H exchanger activity. The results suggest that the Na /H exchanger of X. laevis oocytes can be activated by G proteins and that this activation is not direct but mediated by protein kinase A- and/or protein kinase C-dependent pathways.