Effect of norepinephrine on intracellular pH in kidney proximal tubule: role of Na+-(HCO-3)n cotransport.
We examined the effect of norepinephrine (NE) on intracellular pH (pHi) and activity of Na+ (aNai) in the isolated perfused kidney proximal tubule of Ambystoma, using single-barreled voltage and ion-selective microelectrodes. In control HCO-3 Ringer, addition of 10(-6) M NE to the bath reversibly depolarized the basolateral membrane potential (V1), the luminal membrane potential (V2), and the transepithelial potential difference (V3) and increased pHi by 0. 14 +/- 0.02. These effects were mimicked by isoproterenol but were abolished after pretreatment with SITS or in the absence of CO2/HCO-3. Removal of bath Na+ depolarized V1 and V2, hyperpolarized V3, and decreased pHi. These effects are largely mediated by the electrogenic Na+-(HCO-3)n cotransporter. In the presence of NE, the effects of Na+ removal on membrane potential differences and the rate of change of pHi were significantly smaller. Reducing bath HCO-3 concentration from 10 to 2 mM at constant CO2 (pH 6.8) depolarized V1 and V2, decreased pHi, and lowered aNai. These changes are also due to Na+-(HCO-3)n. In the presence of NE, reducing bath [HCO-3] caused a smaller depolarizations of V1 and V2, and the rate of pHi decrease was significantly reduced. Our results indicate: 1) NE causes an increase in pHi; 2) the NE-induced alkalinization is mediated by a SITS-sensitive and HCO-3-dependent transporter on the basolateral membrane; and 3) in the presence of NE, the reduced effects caused by basolateral HCO-3 changes or Na+ removal are indicative of an inhibitory effect of NE on Na+-(HCO-3)n cotransport.
Departments of Medicine and Physiology, Tulane University, School of Medicine, New Orleans, Louisiana 70112, USA.
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Abdulnour-Nakhoul
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Khuri
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Nakhoul
D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000494:pharmacology; D000557:Ambystoma; D000818:Animals; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology*; D010477:Perfusion; D012964:Sodium / Q000378:metabolism; D027982:Sodium-Bicarbonate Symporters
D002352:Carrier Proteins; D027982:Sodium-Bicarbonate Symporters; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D012964:Sodium; D007545:Isoproterenol; D009638:Norepinephrine