Evidence for functional tachykinin nk1 receptors on human isolated
small bronchi.
Emmanuel, Naline, Mathieu Molimard, Domenico Regoli, Xavier Emonds
-Alt, Jean Fran[cedilla]cois Bellamy, and Charles Advenier.
Laboratoire de Pharmacologie, Facult[acute]e de M[acute]edecine
Paris Ouest, 15, rue de l'Ecole de M[acute]edecine, F-75270 Paris
Cedex 06, France, Service de Pneumologie, H[circumflex]opital St
Louis, 1 avenue Claude Vellefaux, F-75010 Paris, France,
Facult[acute]e de M[acute]edecine, Sherbrooke, Quebec, Canada,
SANOFI, 371 Rue du Professeur Blayac, F-34184 Montpellier Cedex,
France, Centre M[acute]edico-chirurgical du Val d'Or, Saint Cloud,
France
APStracts 3:0114L, 1996.
On human small isolated bronchi (diameter <1 mm), but not on
larger bronchi (diameter 3-5 mm), SP and specific tachykinin NK1
receptor agonists ([[beta]Ala4,Sar9,Met(O2)11]SP(4-11),
[Sar9,Met(O2)11]SP, [Arg6,Sar9,Met(O2)11]SP(6-11) and septide) (10-10
to 10-6 M) produced a concentration-dependent contraction that
occurred at low concentrations (pD2 values of 7.79 to 8.33) and was
characterized by a low intrinsic activity (Emax of 38 to 45% of Emax
induced by acetylcholine 3 mM, in a non-cumulative manner).
Comparison of cumulative and non-cumulative concentration- response
curves to SP and NK1 receptor agonists suggest rapid receptor
desensitization. The substance P (10-8 M)- induced contraction was
inhibited by tachykinin NK1 receptor antagonists (rank order of
potency : SR 140333 > CP-96,345 > RP 67580), but not by the
tachykinin NK2 receptor antagonist SR 48968. Indomethacin (10-6 M)
abolished the SP-induced contraction. Our results suggest that
tachykinin NK1 receptors are present on human small bronchi and that
their stimulation induce a prostanoid-dependent contraction. The
small isolated bronchus is an interesting model of human tissue to
test NK1 receptor antagonists.
Received 13 November 1995; accepted in final form 21 June 1996.
APS Manuscript Number L326-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 July 1996