AJP - Lung Cellular and Molecular Physiology, Vol 269, Issue 6 837-L842, Copyright © 1995 by American Physiological Society
Differential tachykinin receptor subtype activation in capsaicin and KCl contractions of guinea pig trachealis
R. W. Mitchell, I. M. Ndukwu, A. Herrnreiter, K. Uzendoski, B. Gitter, J. Solway and A. R. Leff
Department of Medicine, University of Chicago, Illinois 60637, USA.
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 approximately 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 < 0.05), and treatment with a selective
neurokinin subtype 1 (NK1) receptor antagonist, LY-297911, caused even
greater inhibition of KCl-elicited contraction to 124 +/- 8 %EFS (P <
0.001). By contrast, SR-48968, a selective 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, SR-48968 augmented the inhibition
of contraction caused by LY-297911 to 93 +/- 15 %EFS (P < 0.05 vs.
LY-297911 alone). In contrast to the effect on KCl-induced contraction,
LY-297911 caused only moderate inhibition of the contraction caused by
capsaicin to 81 +/- 13 %EFS (P < 0.05 vs. control, 114 +/- 15 %EFS),
whereas SR-48968 caused substantial attenuation of contraction caused by
capsaicin to 23 +/- 5 %EFS (P < 0.005 vs. LY-297911). We demonstrate
that a significant portion of the contraction caused by KCl, in addition to
capsaicin, 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.
