DIFFERENTIAL TACHYKININ RECEPTOR SUBTYPE ACTIVATION IN CAPSAICIN AND KCL CONTRACTIONS OF GUINEA-PIG TRACHEALIS

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 wa s elicited with similar to 45 mM KCl and was 196 +/- 8% of the respons e to electrical field stimulation (%EFS) in the same tissues. Muscarin ic receptor blockade with atropine modestly attenuated this contractio n caused by KCl to 175 +/- 9 %EFS (P < 0.05), and treatment with a sel ective neurokinin subtype 1 (NK1) receptor antagonist, LY-297911, caus ed even greater inhibition of KCl-elicited contraction to 124 +/- 8 %E FS (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. KC l 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 K Cl-induced contraction, LY-297911 caused only moderate inhibition of t he contraction caused by capsaicin to 81 +/- 13 %EFS (P < 0.05 vs. con trol, 114 +/- 15 %EFS), whereas SR-48968 caused substantial attenuatio n of contraction caused by capsaicin to 23 +/- 5 %EFS (P < 0.005 vs. L Y-297911). We demonstrate that a significant portion of the contractio n caused by KCl, in addition to capsaicin, is elicited in guinea pig T SM through neurokinin secretion. However, NK1 receptors predominantly mediate contraction caused by KCl, and NK2 receptors predominantly med iate contraction elicited by capsaicin in guinea pig airway smooth mus cle.