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Beta-adrenergic regulation of amiloride-sensitive lung sodium channels.
- Source :
-
American journal of physiology. Lung cellular and molecular physiology [Am J Physiol Lung Cell Mol Physiol] 2002 Apr; Vol. 282 (4), pp. L609-20. - Publication Year :
- 2002
-
Abstract
- We investigated the mechanism by which cAMP increases sodium transport in lung epithelial cells. Alveolar type II (ATII) cells have two types of amiloride-sensitive, cation channels: a nonselective cation channel (NSC) and a highly selective channel (HSC). Exposure of ATII cells to cAMP, beta-adrenergic agonists, or other agents that increase adenylyl cyclase activity increased activity of both channel types, albeit by different mechanisms. NSC open probability (P(o)) increased severalfold when exposed to terbutaline, isoproterenol, forskolin, or cAMP analogs without any change in NSC number. In contrast, terbutaline increased HSC number with no significant change in HSC P(o). For both channels, the effect of terbutaline was blocked by propranolol and H-89, suggesting a protein kinase A (PKA) requirement for beta-adrenergic-induced changes in channel activity. Terbutaline increased cAMP levels in ATII cells, but intracellular calcium also increased. Calcium sequestration with BAPTA blocked beta-adrenergic-induced increases in NSC P(o) but did not alter HSC activity. These observations suggest that beta-adrenergic stimulation increases intracellular cAMP and activates PKA. PKA increases HSC number and increases intracellular calcium. The increase in calcium increases NSC P(o). Thus increased cAMP levels are likely to increase lung sodium transport regardless of which channel type is present.
- Subjects :
- Amiloride pharmacology
Animals
Antiporters metabolism
Calcium metabolism
Cells, Cultured
Chelating Agents pharmacology
Colforsin pharmacology
Cyclic AMP metabolism
Cyclic AMP-Dependent Protein Kinase Type II
Cyclic AMP-Dependent Protein Kinases metabolism
Diuretics pharmacology
Egtazic Acid pharmacology
Enzyme Inhibitors pharmacology
Epithelial Cells cytology
Epithelial Cells metabolism
Extravascular Lung Water metabolism
Isoproterenol pharmacology
Isoquinolines pharmacology
Membrane Potentials drug effects
Membrane Potentials physiology
Patch-Clamp Techniques
Pulmonary Alveoli cytology
Rats
Rats, Sprague-Dawley
Receptors, Adrenergic, beta metabolism
Adrenergic beta-Agonists pharmacology
Egtazic Acid analogs & derivatives
Pulmonary Alveoli metabolism
Sodium metabolism
Sodium Channels metabolism
Sulfonamides
Terbutaline pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1040-0605
- Volume :
- 282
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Lung cellular and molecular physiology
- Publication Type :
- Academic Journal
- Accession number :
- 11880285
- Full Text :
- https://doi.org/10.1152/ajplung.00356.2001