Effects of cholecystokinin-8 induced gastric dysmotility on bile regurgitation during stress and molecular mechanisms

Autor: Peng Lv, Hong Xia, Xin-Min Si, He-Sheng Luo, Lei Huang
Rok vydání: 2006
Předmět:
Zdroj: Regulatory Peptides. 136:64-71
ISSN: 0167-0115
DOI: 10.1016/j.regpep.2006.04.016
Popis: To illustrate the existence of bile regurgitation under stress condition, and explore the possible effects and related mechanism of changes of plasma cholecystokinin octapeptide (CCK-8) and intragastric pH on stress-induced bile regurgitation in rats.(1) Changes in plasma CCK-8 and gastric bile concentration were respectively measured by using radioimmunoassay (RIA) method while simultaneously calculating gastric ulcer index (UI) and intragastric pH; (2) Each isolated gastric strips were suspended in a tissue chamber to record the contractile responses by polyphysiograph; (3) The responsiveness of gastric smooth muscle cells (SMCs) to sulfated cholecystokinin octapeptide (CCK-8S) were examined using fura-2-loaded microfluorimetric measurement of intracellular calcium concentration ([Ca(2+)]i); (4) The current of L-type calcium channels (I(CaL)) of SMCs were recorded by patch clamp techniques.(1) Compared with the normal control group, plasma CCK-8 and gastric bile concentration significantly increased during stress (p0.01) and both simultaneously reached the peak at the time point of 2 h after stress; UI and intragastric pH apparently increased (p0.01); (2) Significant changes to CCK-8S were found in the mean contractile amplitude and frequency of circular muscle (CM) and longitudinal muscle (LM) of gastric antrum and pylorus; (3) CCK-8S-evoked significant increase in [Ca(2+)]i (p0.01) could be suppressed by CCK-A receptor (CCK-AR) antagonist; whereas a small but significant increase was still elicited by CCK-8S under condition of the removal of extracellular calcium or by given nifidipine; (4) CCK-8S-intensified calcium current (I(CaL)) apparently inhibited by respective administration of nifidipine, Ca(2+)-ATPase inhibitors or calcium dependent chloride channel (I(Cl-Ca)) blocker (p0.01).Gastric mucosal damage induced by bile regurgitation is closely connected with gastric antrum and pylorus dysmotility evoked by CCK-8 during the stress. CCK-8S-evoked [Ca(2+)]i increase in gastric antrum and pylorus SMC depends on the release of intracellular calcium stores which activates L-type voltage-dependent calcium channels (VDCC) through the activation of calcium dependent chloride channels.
Databáze: OpenAIRE
Externí odkaz: