Role of Na-K-2Cl cotransporter-1 in gastric secretion of nonacidic fluid and pepsinogen.
Na-K-2Cl cotransporter-1 (NKCC) has been detected at exceptionally high levels in the gastric mucosa of several species, prompting speculation that it plays important roles in gastric secretion. To investigate this possibility, we 1) immunolocalized NKCC protein in the mouse gastric mucosa, 2) compared the volume and composition of gastric fluid from NKCC-deficient mice and their normal littermates, and 3) measured acid secretion and electrogenic ion transport by chambered mouse gastric mucosa. NKCC was localized to the basolateral margin of parietal cells, mucous neck cells, and antral base cells. In NKCC-deficient mice, gastric secretions of Na+, K+, Cl-, fluid, and pepsinogen were markedly impaired, whereas secretion of acid was normal. After stimulation with forskolin or 8-bromo-cAMP, chambered corpus mucosa vigorously secreted acid, and this was accompanied by an increase in transmucosal electrical current. Inhibition of NKCC with bumetanide reduced current to resting levels but had no effect on acid output. Although prominent pathways for basolateral Cl- uptake (NKCC) and apical Cl- exit [cystic fibrosis transmembrane conductance regulator (CFTR)] were found in antral base cells, no impairment in gastric secretion was detected in CFTR-deficient mice. Our results establish that NKCC contributes importantly to secretions of Na+, K+, Cl-, fluid, and pepsinogen by the gastric mucosa through a process that is electrogenic in character and independent of acid secretion. The probable source of the NKCC-dependent nonacidic electrogenic fluid secretion is the parietal cell. The observed dependence of pepsinogen secretion on NKCC supports the concept that a nonacidic secretory stream elaborated from parietal cells facilitates flushing of the proenzyme from the gastric gland lumen.
McDaniel
Nichole
N
Div. of Biomedical Sciences, 2226 Webber Hall, Univ. of California, Riverside, CA 92521, USA.
Pace
Amy J
AJ
Spiegel
Stefanie
S
Engelhardt
Regina
R
Koller
Beverly H
BH
Seidler
Ursula
U
Lytle
Christian
C
D000818:Animals; D004573:Electrolytes; D004594:Electrophysiology; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000502:physiology*; D051379:Mice; D020116:Pepsinogen A / Q000378:metabolism; D028021:Sodium-Potassium-Chloride Symporters / Q000502:physiology*; D064506:Solute Carrier Family 12, Member 2
D004573:Electrolytes; C578878:Slc12a2 protein, mouse; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; D020116:Pepsinogen A