Differential tachykinin receptor subtype activation in capsaicin and kcl contractions of guinea pig trachealis. Mitchell, Richard W., Ikeadi M. Ndukwu, Anja Herrnreiter, Kerry Uzendoski, Bruce Gitter, Julian Solway, and Alan R. Leff. Asthma, Allergy, and Immunological Disease Research Center, Section of Pulmonary and Critical Care Medicine, Department of Medicine, and the Committees on Clinical Pharmacology and Cell Physiology, Division of the Biological Sciences, The University of Chicago, Chicago, IL 60637 and Central Nervous System Research Division, Lilly Research Laboratories, Indianapolis, IN 46285.
APStracts 2:0119L, 1995.
We assessed the role of endogenously secreted tachykinins in mediating contraction caused by potassium chloride (KCl) in guinea pig tracheal smooth muscle (TSM) strips in vitro. Maximal isometric contraction was elicited with 45 mM KCl and was 196 +/- 8 % of the response to electrical field stimulation (%EFS) in the same tissues. Muscarinic receptor blockade with atropine modestly attenuated this contraction caused by KCl to 175 +/- 9 %EFS (P &LT0.05), and treatment with a selective neurokinin1-receptor (NK1) antagonist, LY297911, caused even greater inhibition of KCl-elicited contraction to 124 +/- 8 %EFS (P &LT 0.001). By contrast, SR48968, a selective neurokinin2 -receptor (NK2) antagonist, had no effect on contraction caused by KCl (183 +/- 9 %EFS; P = NS vs KCl alone). However, given together at the same concentration, SR48968 augmented the inhibition of contraction caused by LY297911 to 93 +/- 15 %EFS (P &LT 0.05 vs LY297911 alone). In contrast to the effect on KCl-induced contraction, LY297911 caused only moderate inhibition of the contraction caused by capsaicin to 81 +/- 13 %EFS (P &LT 0.05 vs control, 114 15 %EFS), whereas SR48968 caused substantial attenuation of contraction caused by capsaicin to 23 +/- 5 %EFS (P &LT 0.005 vs LY297911). We demonstrate, in addition to capsaicin, that a significant portion of the contraction caused by KCl is elicited in guinea pig TSM through neurokinin secretion. However, NK1-receptors predominantly mediate contraction caused by KCl and NK2-receptors predominantly mediate contraction elicited by capsaicin in guinea pig airway smooth muscle. 

Received 24 October 1994; accepted in final form 6 July 1995.
APS Manuscript Number L306-4.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 18 July 1995.