Muscarinic signaling in ciliated tracheal epithelial cells: dual
effects on ca2+ and ciliary beating.
Salathe, Matthias, Eric J. Lipson, Pedro I. Ivonnet, and Richard J.
Bookman.
From the Department of Molecular & Cellular Pharmacology and the
Division of Pulmonary & Critical Care Medicine, University of
Miami School of Medicine, Miami, Florida 33136
APStracts 3:0146L, 1996.
To examine cholinergic signal transduction pathways that modulate
ciliary beat frequency (CBF), cultured, ovine tracheal epithelial
cells were imaged using a combination of phase contrast (CBF) and
fluorescence (Ca2+) microscopy techniques. In single cells,
acetylcholine (ACh) transiently increased CBF and [Ca2+]i, mainly by
Ca2+ release from internal stores, with a small, delayed contribution
from Ca2+ influx. Nicotinic agonists did not alter CBF or [Ca2+]i
whereas atropine blocked the ACh-stimulated transients consistent
with the involvement of muscarinic receptors. 4-diphenylacetoxy-N
-methylpiperidine methiodide (4-DAMP) was 100 times more potent than
pirenzepine in inhibiting the ACh-induced [Ca2+]i peaks suggesting
that the receptor is an M3 sub-type. Interestingly, after depletion
of intracellular Ca2+ stores by thapsigargin, ACh caused a rapid
transient decrease in both CBF and [Ca2+]i, again with an antagonist
profile of M3 receptors. We conclude that activation of M3 muscarinic
receptors initiates specific signaling pathways that act
simultaneously to increase and decrease [Ca2+]i and CBF.
Received 19 June 1996; accepted in final form 19 August 1996
APS Manuscript Number L188-6.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 19 September 1996