Ae4 (Slc4a9) Anion Exchanger Drives Cl- Uptake-dependent Fluid Secretion by Mouse Submandibular Gland Acinar Cells
| Autor: | Marcelo A. Catalán, Gary E. Shull, Yasna Jaramillo, Yusuke Kondo, James E. Melvin, Frances Liu, Gaspar Peña-Münzenmayer |
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| Rok vydání: | 2014 |
| Předmět: |
inorganic chemicals
Male medicine.medical_specialty Mice 129 Strain Submandibular Gland Saliva secretion Acinar Cells Biochemistry digestive system Mice stomatognathic system Chlorides Internal medicine Membrane Biology medicine Cyclic AMP Animals Secretion Chloride-Bicarbonate Antiporters Transcellular Saliva Molecular Biology Ion transporter Mice Knockout Ion Transport Salivary gland Chemistry urogenital system Cell Biology respiratory system Submandibular gland Cell biology Mice Inbred C57BL stomatognathic diseases Bicarbonates Endocrinology medicine.anatomical_structure Female Cotransporter Intracellular |
| Zdroj: | The Journal of biological chemistry. 290(17) |
| ISSN: | 1083-351X |
| Popis: | Transcellular Cl(-) movement across acinar cells is the rate-limiting step for salivary gland fluid secretion. Basolateral Nkcc1 Na(+)-K(+)-2Cl(-) cotransporters play a critical role in fluid secretion by promoting the intracellular accumulation of Cl(-) above its equilibrium potential. However, salivation is only partially abolished in the absence of Nkcc1 cotransporter activity, suggesting that another Cl(-) uptake pathway concentrates Cl(-) ions in acinar cells. To identify alternative molecular mechanisms, we studied mice lacking Ae2 and Ae4 Cl(-)/HCO3 (-) exchangers. We found that salivation stimulated by muscarinic and β-adrenergic receptor agonists was normal in the submandibular glands of Ae2(-/-) mice. In contrast, saliva secretion was reduced by 35% in Ae4(-/-) mice. The decrease in salivation was not related to loss of Na(+)-K(+)-2Cl(-) cotransporter or Na(+)/H(+) exchanger activity in Ae4(-/-) mice but correlated with reduced Cl(-) uptake during β-adrenergic receptor activation of cAMP signaling. Direct measurements of Cl(-)/HCO3 (-) exchanger activity revealed that HCO3 (-)-dependent Cl(-) uptake was reduced in the acinar cells of Ae2(-/-) and Ae4(-/-) mice. Moreover, Cl(-)/HCO3 (-) exchanger activity was nearly abolished in double Ae4/Ae2 knock-out mice, suggesting that most of the Cl(-)/HCO3 (-) exchanger activity in submandibular acinar cells depends on Ae2 and Ae4 expression. In conclusion, both Ae2 and Ae4 anion exchangers are functionally expressed in submandibular acinar cells; however, only Ae4 expression appears to be important for cAMP-dependent regulation of fluid secretion. |
| Databáze: | OpenAIRE |
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