Calcium Sources Mediating Human Gallbladder Contraction by Acetylcholine end Cholecystokinin

Yoon, Yong Bum; Rhee, Jong Chul; Rhee, Poong Lyul; Lee, Jong Kyun; Kang, Tong Mook; Uhm, Dae Yong

Abstract

BACKGROUND AND AIMS: Gallbladder contraction regulates the bile flow during digestive period and pevents stasis of the lithogenic bile. In addition, abnormal gallbladder motility may cause recurtent biliary pain or biliary dyskinesia. Acetylcholine (ACh) and cholecystokinin (CCK) are major neurohormonal mediators in gallbladder contraction. In addition, an increase in cytosolic calcium concentration is a common event resulting in smooth muscle contraction. This study was designed to identify the sources of calcium utilized in gallbladder smooth muscle contraction mediated by ACh and CCK in human.
METHODS
By measuring the contractile forces of the muscle strips and the intracellular free Ca2+ conentration, Ca2+ sources utilized in muscle contraction were estimated.
RESULTS
The ACh-induced contractile response was accentuated after a twofold increment of the extracellular calcium concentration. The contractile response to ACh was markedly blocked by verapamil (10 p M) and was significantly potentiated by Bay-K 8644 (1 pM). Preventing Ca2+ release from the internal stores by strontium (4 mM) reduced the contractile response to ACh and CCK. The inhibitory effect was greater in the response to CCK than in the response to ACh Depletion of IP3-sensitive calcium stores by a high concentration of hista mine (50 uM) significantly inhibited the contractile response to CCK. The intfacellular caleium concentration was increased slowly on ACh-induced contraction but rapidly on CCK-induced contraction which was similar to the behavior of caffeine.
CONCLUSIONS
These results suggest that ACh utilizes both intracellular and extracellular calcium, mainly extracellular calcium, whereas CCK utilizes calcium frorn intracellular calcium stores.