Journal article
Beta-adrenergic-mediated Cl secretion: evidence for additional non-cAMP-dependent pathway of effect
American journal of physiology. Lung cellular and molecular physiology, Vol.259(6), pp.L426-L431
12/01/1990
DOI: 10.1152/ajplung.1990.259.6.L426
PMID: 2175556
Abstract
It has been suggested that beta-adrenergic receptor antagonists with intrinsic sympathomimetic activity, like pindolol, are weak partial agonists for beta-adrenergic-stimulated adenylyl cyclase activation. To evaluate this possibility, beta-adrenergic-mediated chloride secretion was studied in tracheal epithelial cells maintained in primary culture. Pindolol caused a dose-dependent increase in chloride secretion with a half-maximal effective concentration of 91 pM to a maximum that was 30 +/- 3% that of isoproterenol. Pindolol-induced chloride secretion was antagonized by the beta-adrenergic antagonist nadolol. However, in contrast to isoproterenol, pindolol did not stimulate adenosine 3',5'-cyclic monophosphate (cAMP) accumulation, adenylyl cyclase activity, or protein kinase A activation. Further studies examined the coupling of beta-adrenergic stimulation of cAMP accumulation to beta-adrenergic stimulation of chloride secretion. Coincubation of cells with the phosphodiesterase inhibitor RA233 increased maximal isoproterenol-stimulated cAMP accumulation eightfold but did not significantly increase the potency or maximal effect of isoproterenol for chloride secretion. It is clear that beta-adrenergic-stimulated elevations in cAMP mediate chloride secretion. These studies also demonstrate that pindolol, a drug with intrinsic sympathomimetic activity, mediates a beta-adrenergic receptor-specific increase in chloride secretion without increasing adenylyl cyclase nor protein kinase A activities. Thus intrinsic sympathomimetic activity may represent a non-cAMP-dependent mechanism of beta-adrenergic effect.
Details
- Title: Subtitle
- Beta-adrenergic-mediated Cl secretion: evidence for additional non-cAMP-dependent pathway of effect
- Creators
- Ross D Feldman - Department of Internal Medicine, College of Medicine, University of Iowa, Iowa City 52242Abigail Brotherton - Department of Internal Medicine, College of Medicine, University of Iowa, Iowa City 52242Michael J Welsh - Department of Internal Medicine, College of Medicine, University of Iowa, Iowa City 52242
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Lung cellular and molecular physiology, Vol.259(6), pp.L426-L431
- DOI
- 10.1152/ajplung.1990.259.6.L426
- PMID
- 2175556
- NLM abbreviation
- Am J Physiol Lung Cell Mol Physiol
- ISSN
- 1040-0605
- eISSN
- 1522-1504
- Publisher
- American Physiological Society
- Language
- English
- Date published
- 12/01/1990
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Fraternal Order of Eagles Diabetes Research Center; Neurosurgery; Internal Medicine
- Record Identifier
- 9984020773402771
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