Tachykinin NK 2 receptors predominantly mediate tachykinin-induced contractions in ovine trachea

Abstract

In vitro studies were conducted to characterize the contractile effects of tachykinins in normal ovine trachea with a view in the future to compare tachykinin contractile responses in allergic tissue. Tracheal smooth muscle strips were prepared for in vitro studies of isometric contraction in response to cumulative addition of carbachol, acetylcholine, histamine, neuropeptide gamma, substance P, neurokinin A, neurokinin B, [Sar 9, Met(O 2) 11]substance P, [Nle 10]neurokinin A-(4–10), and [Succinyl-Asp 6, Me-Phe 8]substance P-(6–11) (senktide). The rank order of potency was neuropeptide gamma>carbachol>neurokinin A≥[Nle 10]neurokinin A-(4–10)>acetylcholine≥histamine. Phosphoramidon enhanced the contractile response to neurokinin A and substance P, but not to neuropeptide gamma, [Sar 9, Met(O 2) 11]substance P or senktide. Repeated cumulative concentration responses for acetylcholine, substance P, neurokinin A, [Sar 9, Met(O 2) 11]substance P and histamine were also conducted to test for tachyphylaxis. No tachyphylaxis to acetylcholine, substance P, or neurokinin A was observed, however, [Sar 9, Met(O 2) 11]substance P and histamine did exhibit tachyphylaxis. Atropine had no effect on tracheal contractions to neurokinin A and substance P, while [Sar 9, Met(O 2) 11]substance P contractions were atropine sensitive. Pyrilamine did not affect substance P-induced tracheal smooth muscle contractions, indicating that the response to substance P was not mediated by histamine release. These results show that, in vitro, natural tachykinins induce tracheal smooth muscle contraction predominantly by a direct effect mediated by tachykinin NK 2 receptors, and a small tachykinin NK 1 receptor mediated cholinergic mechanism.