RESUMEN
The sodium bicarbonate cotransporter (NBC1) mediates bicarbonate reabsorption in the renal proximal tubule. NBC1 activity is stimulated by 10% CO2, however, the mechanism is poorly understood. Here, we examined the mechanism of NBC1 regulation by 10% CO2 using an immortalized human proximal tubule cell line (HK2). In cells exposed to 10% CO2, the cotransporter activity (measured as deltapH/min) increased within minutes and this increase was maintained for 6 to 24 h. Early NBC1 stimulation was accompanied by increased NBC1 phosphorylation. Basolateral membrane NBC1 protein increased by 30 min and reached a maximum at 6 h. Increased NBC activity at 6 h was accounted for by increased NBC exocytosis to the basolateral membrane and not by decreased endocytosis. Latruncullin B (an actin cytoskeleton inhibitor) did not prevent CO2-induced stimulation, while nocodazole (a microtubule-disrupting agent) abrogated the stimulatory effect of 10% CO2. A significant increase in NBC1 mRNA expression level was observed at 6 h and maintained for 24 h. Total NBC1 protein increased at 12 to 24 h with 10% CO2 incubation and this effect was blocked by cycloheximide. In summary, the present study demonstrates that early activation of NBC1 activity by 10% CO2 was mediated by NBC1 phosphorylation. The stimulation of cotransporter activity observed at 6 h was due to exocytosis, while the late effect starting from 12 h was accounted for by increased protein synthesis.
Asunto(s)
Actinas/fisiología , Bicarbonatos/metabolismo , Dióxido de Carbono/farmacología , Exocitosis/fisiología , Túbulos Renales Proximales/metabolismo , Simportadores de Sodio-Bicarbonato/metabolismo , Actinas/efectos de los fármacos , Células Cultivadas , Cicloheximida/farmacología , Exocitosis/efectos de los fármacos , Humanos , Concentración de Iones de Hidrógeno , Nocodazol/farmacología , Fosforilación , Inhibidores de la Síntesis de la Proteína/farmacología , ARN Mensajero/metabolismoRESUMEN
A patient with end-stage renal disease developed severe hyperchloremic acidosis (venous serum total CO2 level of 10 mmol/L) after treatment with 16 L of isotonic saline. Analysis of this case and published literature indicates that dilutional acidosis may result when very large volumes of isotonic saline are administered intravenously, especially in patients with impaired or absent renal function.
Asunto(s)
Acidosis/etiología , Fluidoterapia/efectos adversos , Hemodilución/efectos adversos , Fallo Renal Crónico/terapia , Choque Séptico/tratamiento farmacológico , Cloruro de Sodio/administración & dosificación , Anciano , Cloruros/sangre , Hemodilución/métodos , Humanos , Masculino , Diálisis Renal/métodos , Choque Séptico/diagnóstico , Desequilibrio HidroelectrolíticoRESUMEN
An acidic (pH 5.2) pyruvate-based peritoneal dialysis solution or an equally acidic lactate-based counterpart was added to a residual fluid (i.e., peritoneal effluent) obtained from each of 6 continuous ambulatory peritoneal dialysis patients. It was found that the residual fluids were able to raise the pH of the resultant residual fluid/peritoneal dialysis solution mixture to a higher level in the case of the pyruvate-based solution than in the case of the lactate-based one.