Serotonin evoked calcium transients in airway smooth muscle
cells.
Tolloczko, B., Y. L. Jia, and J. G. Martin.
The Seymour Heisler Laboratory of the Montreal Chest Hospital
Research Centre and Meakins-Christie Laboratories, McGill University,
Montreal, Quebec, Canada
APStracts 2:0066L, 1995.
Serotonin (5-HT) is an important mediator of allergic airway narrowing
in several animal species. The present study was designed to
characterize the receptor subtypes that mediate 5-HT induced airway
responses in the rat. To do this we measured calcium transients and
3,5 c-AMP production evoked by 5-HT in cultured rat tracheal smooth
muscle cells as well as 5-HT-induced contractions of isolated
tracheal rings. 5-HT (10-6-10-4 M) triggered a rapid increase in
[Ca2+]i followed by a second phase of sustained, elevated and
sometimes oscillating levels of [Ca2+]i. Sustained, but not peak
[Ca2+]i levels, were dependent on Ca2+ influx but were not attenuated
by nifedipine (10-5M). Oscillations were observed in cells in Ca2+
-free medium suggesting calcium-induced calcium release (CICR)
independent of Ca2+ influx. The effects of 5-HT were inhibited by
thapsigargin (10-6M) and ketanserin (10-7M). In cells incubated with
LY-278,584 (5-HT3 antagonist) and (-)pindolol (5-HT1 antagonist) 5-HT
evoked responses were not significantly different from the control
values. 5-methyltryptamine (5-MT; a ligand with higher affinity for
5-HT2C receptors than "classical" 5-HT2 receptors), elicited
higher responses than dipropyl-5-carboxamidotryptamine (DP-5-CT),
which possesses lower affinity for 5-HT2C receptors than 5-MT, but an
affinity for the "classical" 5-HT2 receptor similar to 5-MT.
5-HT (10-7 M - 10-4 M) had no effect on basal levels of c-AMP, and
10-6 M 5-HT did not change forskolin induced elevations of c-AMP in
the presence or absence of (-)pindolol. 5-HT increased isometric
force of tracheal rings in a concentration dependent manner.
Ketanserin (10-7 M) caused 100% relaxation and (-)pindolol 40%
relaxation of rings precontracted with 5x10-6 M 5-HT. Our data
suggest that in rat airway 5-HT acts via 5-HT2C-like receptors
expressed on smooth muscle cells causing calcium release from
intracellular stores, followed by calcium influx, possibly through
calcium release activated channels.
Received 19 May 1994; accepted in final form 4 April 1995.
APS Manuscript Number L146-4.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 2 May 1995.