|
|
||||||||
AJP - Lung Cellular and Molecular Physiology, Vol 259, Issue 6 426-L431, Copyright © 1990 by American Physiological Society
ARTICLES |
R. D. Feldman, A. Brotherton and M. J. Welsh
Department of Internal Medicine, College of Medicine, University of Iowa, Iowa City 52242.
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.
This article has been cited by other articles:
![]() |
D. W. McGraw, N. Fukuda, P. F. James, S. L. Forbes, A. L. Woo, J. B. Lingrel, D. P. Witte, M. A. Matthay, and S. B. Liggett Targeted transgenic expression of {beta}2-adrenergic receptors to type II cells increases alveolar fluid clearance Am J Physiol Lung Cell Mol Physiol, October 1, 2001; 281(4): L895 - L903. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |