Cholecystokinin induces esophageal longitudinal muscle contraction and transient lower esophageal sphincter relaxation in healthy humans

Abstract

Cholecystokinin (CCK) is known to cause lower esophageal sphincter (LES) relaxation through the activation of inhibitory motor neurons. CCK receptor agonists increase the frequency of transient LES relaxation through a peripheral mechanism. Recent studies show that the longitudinal muscle contraction (LMC)-related axial stretch might play a role in the LES relaxation by activating the mechanosensitive inhibitory motor neurons. The aim of our study was to determine whether the CCK-induced LES relaxation and the characteristics of LMC resemble those seen with spontaneous transient LES relaxation in humans. Nine healthy volunteers (5 Fr, 40 ± 12 yr) received escalating doses of CCK-octapeptide (CCK-8) (5, 10, 20, and 40 ng/kg). All subjects demonstrated a monophasic response to 5 ng/kg of CCK-8. In the majority of subjects, this response consisted of partial LES relaxation. All subjects showed a biphasic response to 40 ng/kg of CCK-8. The latter in most subjects consisted of 1) a period of partial relaxation followed by 2) complete LES relaxation along with crural diaphragm inhibition. The length of the esophagus decreased by 0.9 ± 0.4 cm, and muscle thickness increased by 40 ± 14% to 1.4 ± 0.2 mm ( P < 0.05) during initial partial LES relaxation. During complete LES relaxation there was greater LMC, as demonstrated by an esophageal shortening of 1.9 ± 0.5 cm and an increase in muscle thickness of 100 ± 16% ( P < 0.01). The complete phase 2 LES relaxation typically terminated with a robust after-contraction. Atropine significantly attenuated the CCK-induced esophageal LMC, prevented crural diaphragm inhibition, and abolished the phase 2 complete LES relaxation.NEW & NOTEWORTHY The phenotypic features of CCK-induced longitudinal muscle contraction (LMC), complete lower esophageal sphincter (LES) relaxation, and crural diaphragm inhibition, followed by a robust after-contraction, resemble those seen during spontaneous transient LES relaxation. A strong temporal relationship between the LMC and complete transient LES relaxation supports our hypothesis that the LMC plays an important role in the LES relaxation and crural diaphragmatic inhibition.