Vip inhibits basal and histamine-stimulated proliferation of human
airway smooth muscle cells.
Maruno, Kaname, Afaf Absood, and Sami I. Said.
Department of Veterans Affairs Medical Center, Northport, NY, and
University Medical Center, Stony Brook, NY 11794-8172
APStracts 2:0049L, 1995.
Airway smooth muscle (ASM) cell proliferation contributes to increased
airway resistance in bronchial asthma. We have examined the
modulation of ASM proliferation by vasoactive intestinal peptide
(VIP), a co-transmitter of airway relaxation. Human ASM cells were
grown in culture as a monolayer. VIP (1.0 nM - 1.0 [mu]M) dose
-dependently inhibited proliferation by up to 82% on day 2, but the
related peptide glucagon had no effect. Histamine (100 nM - 100
[mu]M) increased cell counts by 66%, but in the presence of VIP, cell
counts and [3H]thymidine incorporation were reduced by up to 55%.
Cyclic (c) AMP-promoting agents, including isobutyl methyl-xanthine,
forskolin and 8-bromo-cAMP, alone and especially combined with VIP,
reduced cell counts and [3H]thymidine incorporation, in correlation
with cAMP levels. KT5720 (1.0 nM - 1.0 [mu]M), a selective inhibitor
of cAMP-dependent protein kinase (A kinase), abolished the inhibitory
effect of VIP. The results show that VIP selectively and potently
inhibits human ASM cell growth and multiplication, and nullifies the
mitogenic effect of histamine, by an A kinase-mediated mechanism. A
deficiency of VIP may lead to ASM hyperplasia due to unopposed
stimulation by endogenous mitogens.
Received 18 November 1994; accepted in final form 24 March 1995.
APS Manuscript Number L332-4.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 10 April 1995.