Tachykinins contribute to nerve-mediated contractions in the human esophagus

Background & Aims: Tachykinins mediate nonadrenergic, noncholinergic excita tion in the gastrointestinal tract, but their role in esophageal peristalsi s 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 contract ions. Isometric tension responses to agonists or electrical field stimulati on were recorded in circular and longitudinal muscle strips, Results: Tachy kinins produced concentration-dependent increases in tension in circular an d longitudinal muscle strips, with the following order of potency: beta -Al a(8)-neurokinin (NH) A (4-10) > NHB > substance P, suggesting NK2 receptor involvement. The NK2 receptor antagonist, SR48968 (1 mu mol/L), inhibited r esponses to tachykinins in both muscles. Nerve activation produced on- and off-contractions in circular muscle and a duration-contraction in longitudi nal muscle. Atropine (10 mu mol/L)-insensitive nerve-evoked contractions we re identified for the 3 types of responses. SR48968 produced concentration- dependent inhibition of atropine-insensitive on- and off-contractions but h ad no effect on the duration-contraction. At low stimulus frequency (1 Hz), on-contractions showed greater sensitivity to SR48968 than off-contraction s. Conclusions: Nerve-mediated contractions in the human esophagus have a s ignificant atropine-insensitive component. Tachykinins acting on NK2 recept ors can account for some, but not all, of this response, suggesting that ot her excitatory mechanisms also contribute.