Endothelin-1 cooperates with epidermal growth factor to induce
mitogenesis via a ptx-sensitive pathway in airway smooth muscle
cells.
Fujitani, Yasushi, and Claude Bertrand.
Department of Respiratory Diseases and Allergy, Ciba-Geigy Ltd.,
CH-4002 Basel Switzerland
APStracts 3:0400C, 1996.
We have examined the mitogenic effect of endothelin-1 (ET-1) alone or
in combination with EGF in cultured airway smooth muscle cells from
guinea-pig (ASM). ET-1 showed a weak mitogenic activity compared to
the effect of EGF. However, when ET-1 and EGF were applied
simultaneously, ET-1 synergistically enhanced the mitogenic activity
of EGF. Neither inhibition of phospholipase C[beta] nor depletion of
protein kinase C affected this synergism. On the other hand,
pertussis toxin (PTX), a Gi protein inhibitor, abolished the
synergistic effect of ET-1 on EGF-induced mitogenesis. ET-1 induced a
transient MAP kinase activation peaking at 5 min. In contrast, EGF
induced a stronger signal that was maintained up to 20 min. However,
concomitant stimulation of ASM with ET-1 and EGF caused an enhanced
MAP kinase activation compared to EGF alone. Moreover, PTX abolished
the enhanced MAP kinase activation observed in this condition. These
results indicate that ET-1 can interact with EGF-induced mitogenic
axis through the Gi protein dependent pathway, which is distinct from
its direct mitogenic pathway.
Received 27 August 1996; accepted in final form 4 December 1996.
APS Manuscript Number C502-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996