Carbonic Anhydrase II and Alveolar Fluid Reabsorption during Hypercapnia

Abstract

IllinoisCarbonic anhydrase II (CAII) plays an important role in carbon dioxide metabolism and intracellular pH regulation. In this study, we provide evidence that CAII is expressed in both type I (AECI) and type II (AECII) alveolar epithelial cells by RT-PCR and Western blotting in freshly isolated rat cells. These results were further confirmed by double immunostaining with CAII antibodies and AECI-or AECII-specific markers in freshly isolated alveolar epithelial cells and rat lung tissues. Inhibition of CAII by acetazolamide or methazolamide delayed the decrease in the intracellular pH observed during hypercapnia in cultured AECI, AECII, and AECI-like cells. In an isolated-perfused rat lung model, alveolar fluid reabsorption significantly decreased during high CO 2 exposure, which was not prevented by carbonic anhydrase inhibition. Thus, we provide evidence that CAII is expressed in rat alveolar epithelial cells and does not regulate lung alveolar fluid reabsorption during hypercapnia.

AMP-activated protein kinase regulates CO2-induced alveolar epithelial dysfunction in rats and human cells by promoting Na,K-ATPase endocytosis

“…CO 2 -induced Na,K-ATPase endocytosis is mediated by AMPK. We have recently observed that hypercapnia leads to AFR impairment and promotes Na,K-ATPase endocytosis from the plasma membrane to the intracellular compartments in AECs (21,23). To determine whether activation of AMPK was required for the hypercapniainduced Na,K-ATPase endocytosis, we assessed plasma membrane Na,K-ATPase protein abundance in ATII cells exposed to high CO 2 in the presence of the AMPK inhibitor compound C. Exposure of cells to 120 mmHg CO 2 decreased the plasma membrane Na,K-ATPase α 1 protein abundance by approximately 45% without affecting the total Na,K-ATPase cell pools.…”

The physiological and molecular effects of elevated CO2levels

“…29,30 These effects of hypercapnia on the alveolar epithelia are not due to hypoxia and can be reversed by the treatment of rats with beta-adrenergic agonists. 31 Significant progress has been made in understanding the mechanisms by which high CO 2 levels lead to impaired alveolar fluid reabsorption (Fig. 1).…”

Immunohistochemical Localization and Gene Expression of Carbonic Anhydrase Isoenzymes CA-II and CA-VI in Canine Lower Airways and Lung

“…, Motoharu OISHI 1) , Tomoko AMASAKI 4) , Satoshi SOETA 5) , Nobutsune ICHIHARA 1) , Toshiho NISHITA 2) , Masaru MURAKAMI 3) , Hajime AMASAKI 5) and Masao ASARI 1) * 1) Departments of Anatomy, 2) Carbonic anhydrase (CA; EC4.2.1.1) is a zinc-containing metalloenzyme that has many functions, including macromolecule stabilization, gas exchange, acid-base balance, ion transport, and bone resorption [17]. About 14 CA isoenzymes are widely distributed in almost all mammalian species [4].…”

“…The immunohistochemical distribution of CA-II has been determined in the respiratory system of humans [15] and rats [2], while that of CA-VI has been reported for mice [7] and rats [8]. Recently, canine CA-VI was detected in the upper respiratory tract, in particular, in the nasal cavity [16].…”

“…However, in our dogs, some respiratory epithelial and great alveolar cells in the lung showed weak immunopositivity to both CAs. Recently, the respiratory epithelial cells and great alveolar cells in rats were reported to be immunopositive for CA-II [2,3]. Thus, the immunoreactivities of the CAs appear to differ between animals based on respiratory function.…”