Tachykinins contribute to nerve-mediated contractions in the human esophagus

Background & Aims: Tachykinins mediate nonadrenergic, noncholinergic excitation in the gastrointestinal tract, but their role in esophageal peristalsis remains unclear, Methods: We used muscle strips from the distal third of human esophagus, obtained from patients undergoing esophagectomy for cancer, to investigate the contribution of tachykinins to nerve-mediated contractions. Isometric tension responses to agonists or electrical field stimulation were recorded in circular and longitudinal muscle strips, Results: Tachykinins produced concentration-dependent increases in tension in circular and longitudinal muscle strips, with the following order of potency: beta -Ala(8)-neurokinin (NH) A (4-10) > NHB > substance P, suggesting NK2 receptor involvement. The NK2 receptor antagonist, SR48968 (1 mu mol/L), inhibited responses to tachykinins in both muscles. Nerve activation produced on- and off-contractions in circular muscle and a duration-contraction in longitudinal muscle. Atropine (10 mu mol/L)-insensitive nerve-evoked contractions were identified for the 3 types of responses. SR48968 produced concentration-dependent inhibition of atropine-insensitive on- and off-contractions but had no effect on the duration-contraction. At low stimulus frequency (1 Hz), on-contractions showed greater sensitivity to SR48968 than off-contractions. Conclusions: Nerve-mediated contractions in the human esophagus have a significant atropine-insensitive component. Tachykinins acting on NK2 receptors can account for some, but not all, of this response, suggesting that other excitatory mechanisms also contribute.