Na/H- and Cl/OH-exchange in rat jejunal and rat proximal tubular brush border membrane vesicles

The Na + /H + exchanger 3 (NHE3) is expressed in the brush border membrane (BBM) of proximal tubules (PT). Its activity is down-regulated on increases in intracellular cAMP levels. The aim of this study was to investigate the contribution of the protein kinase A (PKA) and the exchange protein directly activated by cAMP (EPAC) dependent pathways in the regulation of NHE3 by adenosine 3′,5′-cyclic monophosphate (cAMP). Opossum kidney cells and murine kidney slices were treated with cAMP analogs, which selectively activate either PKA or EPAC. Activation of either pathway resulted in an inhibition of NHE3 activity. The EPAC-induced effect was independent of PKA as indicated by the lack of activation of the kinase and the insensitivity to the PKA inhibitor H89. Both PKA and EPAC inhibited NHE3 activity without inducing changes in the expression of the transporter in BBM. Activation of PKA, but not of EPAC, led to an increase of NHE3 phosphorylation. In contrast, activation of PKA, but not of EPAC, inhibited renal type IIa Na + -coupled inorganic phosphate cotransporter (NaPi-IIa), another Na-dependent transporter expressed in proximal BBM. PKA, but not EPAC, induced the retrieval of NaPi-IIa from BBM. Our results suggest that EPAC activation may represent a previously unrecognized mechanism involved in the cAMP regulation of NHE3, whereas regulation of NaPi-IIa is mediated by PKA but not by EPAC.

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“…35. Measurements were performed in a Shimadzu RF-5000 spectrofluometer equipped with a thermostatized cuvette (kept at 25°C).…”

Section: Resultsmentioning

confidence: 99%

Regulation of sodium-proton exchanger isoform 3 (NHE3) by PKA and exchange protein directly activated by cAMP (EPAC)

Honegger

Capuano

Winter

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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“…Subsequent studies in isolated apical membrane vesicles have disagreed with respect to the presence or absence of C1/OH exchange (9)(10)(11)(12)(13)(14)(15). Karniski and Aronson (16) found rapid Cl/formate exchange in these apical membranes.…”

Section: Introductionmentioning

confidence: 99%

Apical membrane chloride/base exchange in the rat proximal convoluted tubule.

Alpern¹

1987

J. Clin. Invest.

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To examine whether Cl/base exchange is present on the apical membrane of the proximal convoluted tubule, cell pH was measured fluorometrically in the in vivo microperfused rat proximal tubule with (2',7')-bis(carboxyethyl)-(5,6)-carboxyfluorescein.The effect of luminal chloride addition was examined in tubules perfused symmetrically with chloride-free solutions. In the absence of inhibitors, luminal chloride addition did not affect cell pH. However, after inhibition of basolateral membrane anion transport with peritubular 4-acetamido-4'-isothiocyano-(2,2')-disulfonic-stilbene (to amplify effects of apical membrane transport on cell pH), luminal chloride addition caused a small cell acidification (delta pH, = 0.02). When 1 mM formate was added to the solutions, luminal chloride addition caused a larger change in cell pH (delta pH, = 0.06) that was inhibited by (4,4')-diisothiocyano-(2,2')-disulfonic-stilbene. This stimulation of Cl/base exchange was not seen with 1 mM acetate addition. These results demonstrate apical membrane Cl/base exchange, a significant fraction of which is dependent on the presence of formate and probably represents Cl/formate exchange.

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“…The presence of the Na+/H+ antiport in intestinal brush border membrane has been shown by several groups (MURER et al, 1976;KNICKELBEIN et al, 1983;CASSANO, 1984). The Na+/H+ antiport is known to be regulated by intracellular pH, namely, acidification of intracellular fluid stimulates it while alkalinization inhibits this mechanism (ARONSON et al, 1982).…”

Section: Discussionmentioning

confidence: 99%

Sodium-independent, hydrogen ion-dependent changes in membrane potential and conductance induced by dipeptides in Triturus enterocytes.

Shimada

Hoshi

1986

Jpn.J.Physiol

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The effects of Na+ and pH in the medium on dipeptide transport across Triturus small intestinal brush border membrane were studied electrophysiologically. Although glycylglycine exists mainly in the zwitterionic form at pH 7.30, it induced marked depolarization in the membrane potential and reduction in the input resistance both in the presence and absence of Na+ in the medium. Similar Na + -independent depolarization and resistance change were also observed with L-carnosine. On the contrary, glycine induced membrane depolarization and reduction in the input resistance only in the presence of Na + in the medium. When pH of the medium was lowered to 6.00, the magnitude of the depolarization induced by glycylglycine increased by 33%, while at pH 8.30, it decreased by 39%. These data indicate that dipeptide transport across the intestinal brush border membrane is coupled with H + and has no direct interaction with Na + .

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Na/H- and Cl/OH-exchange in rat jejunal and rat proximal tubular brush border membrane vesicles

Cited by 62 publications

References 26 publications

Regulation of sodium-proton exchanger isoform 3 (NHE3) by PKA and exchange protein directly activated by cAMP (EPAC)

Regulation of sodium-proton exchanger isoform 3 (NHE3) by PKA and exchange protein directly activated by cAMP (EPAC)

Apical membrane chloride/base exchange in the rat proximal convoluted tubule.

Sodium-independent, hydrogen ion-dependent changes in membrane potential and conductance induced by dipeptides in Triturus enterocytes.

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