Tachykinins induce gelatinase production by guinea pig alveolar
macrophages involvement of nk2 receptors.
D'ortho, Marie-Pia, Pierre-Henri Jarreau, Christophe Delacourt, Sophie
Pezet, Chantal Lafuma, Alain Harf, and Isabelle Macquin-Mavier.
D[acute]epartement de Physiologie, Service de Pharmacologie
Clinique and Institut National de la Sant[acute]e et de la Recherche
M[acute]edicale INSERM U 296, Facult[acute]e de M[acute]edecine,
94010 Cr[acute]eteil, France
APStracts 2:0132L, 1995.
To determine whether tachykinins induce gelatinase production by
guinea pig alveolar macrophages (AMACs), and to characterize the
mechanism involved, we incubated AMACs with substance?P (SP),
neurokinin A (NKA) or the N-terminal fragment of SP, SP(1-7). The
effects of increasing concentrations of selective NK1 and NK2
agonists on tachykinin induced gelatinase production were also
evaluated, as were the effects of a selective NK2 antagonist.
Gelatinase activity in conditioned culture media (CCM) was assessed
by zymography and quantified by image analysis. SP increased 92-kDa
gelatinase activity in CCM of AMACs concentration-dependently, with a
maximum increase at 10-4M. NKA, the N-terminal fragment of SP, and an
NK1 selective agonist had no effect. In contrast, a selective
NK2?agonist induced a concentration-dependent increase in gelatinase
activity. The increase in this activity induced by SP and the
selective NK2 agonist was inhibited by a selective NK2 antagonist. We
conclude that SP induces gelatinase production by alveolar
macrophages through NK2 receptor activation. The release of
gelatinase may constitute one mechanism through which SP contributes
to the epithelial lesions observed in bronchial hyperreactivity and
asthma.
Received 30 January 1995; accepted in final form 10 July 1995.
APS Manuscript Number L28-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 14 August 1995.