Acute regulation of Na/H exchanger NHE3 by adenosine A(1) receptors is mediated by calcineurin homologous protein.

Adenosine is an autacoid that regulates renal Na(+) transport. Activation of adenosine A(1) receptor (A(1)R) by N(6)-cyclopentidyladenosine (CPA) inhibits the Na(+)/H(+) exchanger 3 (NHE3) via phospholipase C/Ca(2+)/protein kinase C (PKC) signaling pathway. Mutation of PKC phosphorylation sites on NHE3 does not affected regulation of NHE3 by CPA, but amino acid residues 462 and 552 are essential for A(1)R-dependent control of NHE3 activity.

Bimodal acute effects of A1 adenosine receptor activation on Na+/H+ exchanger 3 in opossum kidney cells.

Regulation of renal apical Na+/H+ exchanger 3 (NHE3) activity by adenosine has been suggested to contribute to acute control of mammalian Na(+) homeostasis. The mechanism by which adenosine controls NHE3 activity in a renal cell line was examined. The adenosine analog, N(6)-cyclopentyladenosine (CPA) exerts a bimodal effect on NHE3: CPA concentrations >10(-8) M inactivate NHE3, whereas concentrations <10(-8) M stimulate NHE3 activity.

Molecular aspects of acute inhibition of Na(+)-H(+) exchanger NHE3 by A(2)-adenosine receptor agonists.

Adenosine regulates Na(+) homeostasis by its acute effects on renal Na(+) transport. We have shown in heterologously transfected A6/C1 cells (renal cell line from Xenopus laevis) that adenosine-induced natriuresis may be effected partly via A(2) adenosine receptor-mediated inactivation of the renal brush border membrane Na(+)-H(+) exchanger NHE3. In this study we utilized A6/C1 cells stably expressing wild-type as well as mutated forms of NHE3 to assess the molecular mechanism underlying A(2)-dependent control of NHE3 function.

The Na+/H+ exchanger gene family.

Na+/H+ exchangers (NHEs) extrude protons from, and take up sodium ions into cells. Six isoforms, NHE-1 - NHE-6, have been cloned. NHE proteins are composed of an N-terminal domain, which most likely crosses the cell membrane 12 times and constitutes the cation exchange machinery, and a C-terminal tail, which modulates the exchanger by interacting with protein kinases and regulatory factors.