High-mobility group box 1 (HMGB1) is a nuclear protein released extracellularly in response to infection or injury, where it activates immune responses and contributes to the pathogenesis of kidney dysfunction in sepsis and sterile inflammatory disorders. Recently, we demonstrated that HMGB1 inhibits HCO3 (-) absorption in perfused rat medullary thick ascending limbs (MTAL) through a basolatera...

In humans and terrestrial vertebrates, the kidney controls systemic pH in part by absorbing filtered bicarbonate in the proximal tubule via an electrogenic Na+/HCO3- cotransporter (NBCe1/SLC4A4). Recently, human genetics revealed that NBCe1 is the major renal contributor to this process. Homozygous point mutations in NBCe1 cause proximal renal tubular acidosis (pRTA), glaucoma, and cataracts (I...

During perfusion of a plasma-like solution, colonic absorption rate of chloride was much higher than the secretion rate of bicarbonate (34 vs. 3.5 meq/h, respectively). This might suggest that anion exchange (Cl/HCO3) accounts for only a small fraction of total chloride absorption. However, if the colon absorbs as well as secretes bicarbonate, this reasoning would underestimate the magnitude of...

The inner stripe of the outer medullary collecting tubule is a major distal nephron segment in urinary acidification. To examine the mechanism of basolateral membrane H+/OH-/HCO3- transport in this segment, cell pH was measured microfluorometrically in the inner stripe of the rabbit outer medullary collecting tubule perfused in vitro using the pH-sensitive fluorescent dye, (2',7')-bis(carboxyet...

Canalicular bile formation is a complex process that involves basolateral and apical cell membrane transport, paracellular transport and vesicular transport, all of which may be subject to regulation by pH. We review the concept that apical cell membrane bicarbonate secretion promotes bile salt independent canalicular bile formation. We show that the presence of paracellular electrolyte transpo...

Micropuncture techniques have been used to study electrolyte secretion by the spontaneously secreting in vitro rabbit pancreas over a wide range of environmental conditions. Pancreatic secretion does not have a strong requirement for HCO3 and secretion continues at nearly normal rates when exogenous HCO3 is replaced by acetate. Acetate concentration in the juice averages 70 meq/liter, nearly th...

absorption in rabbit outer medullary collecting duct: role of luminal carbonic anhydrase. Am. J. Physiol. 274 (Renal Physiol. 43): F139–F147, 1998.—Membrane-bound luminal carbonic anhydrase (CA) IV, by catalyzing the dehydration of carbonic acid into CO2 plus water, facilitates H1 secretion in the renal outer medullary collecting duct from the inner stripe (OMCDi). To examine the role of CA IV ...

In a search for the HCO3 supply mechanisms to the enterocyte we cloned and sequenced an intestinal subtype of the NaHCO3 cotransporter isoform I (dNBC1), which turned out to be identical to the pancreatic NBC1 subtype (pNBC1). Within the intestine, we found particularly high NBC1 expression levels in the duodenum and proximal colon. Experiments with stripped rabbit duodenum in Ussing-chambers r...

Bacterial infection of the kidney is associated with renal tubule dysfunction and dysregulation of systemic electrolyte balance. Whether bacterial molecules directly affect renal tubule transport is unknown. We examined the effects of LPS on HCO3(-) absorption in the isolated rat and mouse medullary thick ascending limb (MTAL). LPS decreased HCO3(-) absorption when added to bath or lumen. The M...