Regulation of Renal Na-HCO3 Cotransporter: VIII. Mechanism of Stimulatory Effect of Respiratory Acidosis |
| |
Authors: | OS Ruiz YY Qiu LJ Wang LR Cardoso JAL Arruda |
| |
Institution: | (1) Section of Nephrology, University of Illinois at Chicago and West Side VA Medical Center, Chicago, IL 60612-7315, USA, US |
| |
Abstract: | We examined the effect of respiratory acidosis on the Na-HCO3 cotransporter activity in primary cultures of the proximal tubule of the rabbit exposed to 10% CO2 for 5 min, 2, 4, 24 and 48 hr. Cells exposed to 10% CO2 showed a significant increase in Na-HCO3 cotransporter activity (expressed as % of control levels, 5 min: 142 ± 6, 2 hr: 144 ± 13, 4 hr: 145 ± 11, 24 hr: 150 ± 15,
48 hr: 162 ± 24). The increase in activity was reversible after 48 hr. The role of protein kinase C (PKC) on the stimulatory
effect of respiratory acidosis on the cotransporter was examined in presence of PKC inhibitor calphostin C or in presence
of PKC depletion. Both calphostin C and PKC depletion prevented the effect of 10% CO2 for 5 min or 4 hr to increase the activity of the cotransporter. 10% CO2 for 5 min or 4 hr increased total and particulate fraction PKC activity. To examine the role of phosphotyrosine kinase (PTK)
on the increase in cotransporter activity we studied the effect of two different inhibitors, 2-hydroxy-5-(2,5-dihydroxylbenzyl)
aminobenzoic acid (HAC) and methyl 2,5-dihydroxycinnamate (DHC) which inhibit phosphotyrosine kinase in basolateral membranes.
Cells were pretreated either with vehicle or HAC or DHC and then exposed to 10% CO2 for 5 min or 4 hr. In cells treated with vehicle, 10% CO2 significantly increased cotransporter activity as compared to control cells exposed to 5% CO2. This stimulation by 10% CO2 was completely prevented by HAC or DHC at 5 min (5% CO2: 1.8 ± 0.2, 10% CO2: 2.6 ± 0.2, 10% CO2+ HAC: 1.6 ± 0.2, 10% CO2: +DHC: 2.0 ± 0.3 pH unit/min) and also at 4 hr. The protein synthesis inhibitors actinomycin D and cycloheximide appear to
prevent the effect of 10% CO2 for 4 hr on the cotransporter. Our results show that early respiratory acidosis stimulates the Na-HCO3 cotransporter through PKC and PTK-dependent mechanisms and the late effect appears to be mediated through protein synthesis.
Received: 28 March 1997/Revised: 22 December 1997 |
| |
Keywords: | : Na-HCO3 cotransporter — Respiratory acidosis — Protein kinase C — Phosphotyrosine kinase |
本文献已被 SpringerLink 等数据库收录! |
|