Poston G J, Singh P, Draviam E, Yao C Z, Gomez G, Thompson J C
Department of Surgery, University of Texas Medical Branch, Galveston, Texas 77555-0527.
Dig Dis Sci. 1992 Aug;37(8):1236-44. doi: 10.1007/BF01296566.
The purpose of this study was to measure differences in gallbladder sensitivity to cholecystokinin (CCK) in vivo during the early stages of gallstone formation and to correlate these findings to gallbladder CCK receptors. Guinea pigs were placed on either a normal diet or a two-week cholelithogenic diet, after which gallbladder emptying pressure to exogenously administered CCK was measured in vivo, according to the presence or absence of gallstones. At all doses of CCK tested (except 10(-10) mol/kg), the gallbladder response to CCK of guinea pigs that did not develop gallstones (on the cholelithogenic diet) was more sensitive than that of guinea pigs that did develop gallstones. Neither group was different from guinea pigs on a normal diet. In a second experiment, CCK receptors were measured on gallbladder muscularis from guinea pigs after two weeks on the same diet as in the first experiment. Those guinea pigs that did not develop gallstones had greater concentrations of CCK receptors (149 +/- 9 fmol/mg protein) than those that did develop gallstones (70 +/- 23 fmol/mg protein). Neither group was different from normal diet guinea pigs (119 +/- 57 fmol/mg protein). At the time point measured, there were no differences in the lipid chemistry or protein concentrations of gallbladder bile between the guinea pigs on the cholelithogenic diet that did or did not develop gallstones, or those on normal guinea pig chow. We conclude that the early stages of gallstone formation in guinea pigs are associated with decreased gallbladder sensitivity to CCK and that this change may be due to a lower concentration of CCK receptors on the gallbladder smooth muscle.
本研究的目的是测量在胆结石形成早期体内胆囊对胆囊收缩素（CCK）的敏感性差异，并将这些发现与胆囊CCK受体相关联。将豚鼠分为正常饮食组或为期两周的致石饮食组，之后根据有无胆结石，在体内测量外源性给予CCK后胆囊的排空压力。在所有测试的CCK剂量下（除了10^(-10) mol/kg），未形成胆结石的豚鼠（接受致石饮食）对CCK的胆囊反应比形成胆结石的豚鼠更敏感。两组与正常饮食的豚鼠均无差异。在第二个实验中，对与第一个实验相同饮食两周后的豚鼠胆囊肌层的CCK受体进行测量。未形成胆结石的豚鼠的CCK受体浓度（149±9 fmol/mg蛋白质）高于形成胆结石的豚鼠（70±23 fmol/mg蛋白质）。两组与正常饮食的豚鼠均无差异（119±57 fmol/mg蛋白质）。在所测量的时间点，接受致石饮食但未形成胆结石的豚鼠、形成胆结石的豚鼠以及正常豚鼠饲料喂养的豚鼠之间，胆囊胆汁的脂质化学或蛋白质浓度均无差异。我们得出结论，豚鼠胆结石形成的早期阶段与胆囊对CCK的敏感性降低有关，并且这种变化可能是由于胆囊平滑肌上CCK受体浓度较低所致。
