Transepithelial HCO3- absorption is defective in renal thick ascending limbs from Na+/H+ exchanger NHE1 null mutant mice
| Autor: | Bruns A. Watts, David W. Good, Gary E. Shull, Thampi George, Jamie W. Meyer |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
medicine.medical_specialty
Sodium-Hydrogen Exchangers Physiology Ratón Sodium medicine.medical_treatment chemistry.chemical_element Absorption (skin) Absorption Amiloride Mice Internal medicine Nerve Growth Factor medicine Animals Cation Transport Proteins Mice Knockout Kidney Medulla Sodium-Hydrogen Exchanger 1 Growth factor Osmolar Concentration Membrane Proteins Null mutant Arginine Vasopressin Sodium–hydrogen antiporter Bicarbonates Kinetics Endocrinology Nerve growth factor chemistry Loop of Henle medicine.drug |
| Zdroj: | American journal of physiology. Renal physiology. 287(6) |
| ISSN: | 1931-857X |
| Popis: | In the medullary thick ascending limb (MTAL) of rat kidney, inhibiting basolateral Na+/H+ exchange with either amiloride or nerve growth factor (NGF) results secondarily in inhibition of apical Na+/H+ exchange, thereby decreasing transepithelial HCO3− absorption. To assess the possible role of the Na+/H+ exchanger NHE1 in this regulatory process, MTALs from wild-type and NHE1 knockout (NHE1−/−) mice were studied using in vitro microperfusion. The rate of HCO3− absorption was decreased 60% in NHE1−/− MTALs (15.4 ± 0.5 pmol·min−1·mm−1 wild-type vs. 6.0 ± 0.5 pmol·min−1·mm−1 NHE1−/−). Transepithelial voltage, an index of the NaCl absorption rate, did not differ in wild-type and NHE1−/− MTALs. Basolateral addition of 10 μM amiloride or 0.7 nM NGF decreased HCO3− absorption by 45–49% in wild-type MTALs but had no effect on HCO3− absorption in NHE1−/− MTALs. Inhibition of HCO3− absorption by vasopressin and stimulation by hyposmolality, both of which regulate MTAL HCO3− absorption through primary effects on apical Na+/H+ exchange, were similar in wild-type and NHE1−/− MTALs. Thus the regulatory defect in NHE1−/− MTALs is specific for factors (bath amiloride and NGF) shown previously to inhibit HCO3− absorption through primary effects on basolateral Na+/H+ exchange. These findings demonstrate a novel role for NHE1 in transepithelial HCO3− absorption in the MTAL, in which basolateral NHE1 controls the activity of apical NHE3. Paradoxically, a reduction in NHE1-mediated H+ extrusion across the basolateral membrane leads to a decrease in apical Na+/H+ exchange activity that reduces HCO3− absorption. |
| Databáze: | OpenAIRE |
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