Miyamoto T, Itoh M, Noguchi Y, Yokochi K
First Department of Medicine, Nagoya City University Medical School, Japan.
Gut. 1992 Jan;33(1):21-5. doi: 10.1136/gut.33.1.21.
Both carbachol (10(-4)-10(-3) mol/l) and cholecystokinin octapeptide (CCK-8) (10(-8)-10(-6) mol/l) significantly stimulated the release of pepsinogen from rabbit gastric mucosa maintained in organ culture (213-216% and 143-261% of control, respectively, p less than 0.05-0.01). The secretion was not affected by removing Ca2+ from the culture medium with ethylene glycol tetra-acetic acid. Verapamil failed to inhibit the secretion of pepsinogen induced by the drugs in ordinary culture medium containing Ca2+. In contrast, nicorandil (10(-6)-10(-4) mol/l) attenuated the release of pepsinogen by the drugs in a dose dependent manner, regardless of the presence or absence of Ca2+ in the culture medium. W-7 (10(-6)-10(-4) mol/l) and W-5 (10(-5) and 10(-4), or 10(-6) mol/l) reduced significantly the secretion of pepsinogen induced by carbachol (53-71% and 63-81% of control, respectively, p less than 0.05-0.01) and that by CCK-8 (49-67% and 66-76% of control, respectively, p less than 0.01) in the Ca2+ containing medium. However, W-7 did not show significant inhibition of cyclic adenosine monophosphate (cAMP) and forskolin induced pepsinogen secretion. These findings indicate that the calmodulin messenger branch that is activated by a rise of intracellular Ca2+ mobilised in cytosol from its intracellular, but not extracellular, source plays a critical role in pepsinogen secretion induced by carbachol and CCK-8. It seems likely that an increase in cAMP in cytosol does not provoke any calmodulin mediated pepsinogen secretion.
卡巴胆碱（10⁻⁴ - 10⁻³mol/l）和胆囊收缩素八肽（CCK - 8）（10⁻⁸ - 10⁻⁶mol/l）均能显著刺激器官培养的兔胃黏膜释放胃蛋白酶原（分别为对照组的213 - 216%和143 - 261%，p < 0.05 - 0.01）。用乙二醇四乙酸从培养基中去除Ca²⁺后，该分泌不受影响。维拉帕米未能抑制含Ca²⁺的普通培养基中药物诱导的胃蛋白酶原分泌。相比之下，尼可地尔（10⁻⁶ - 10⁻⁴mol/l）以剂量依赖方式减弱药物诱导的胃蛋白酶原释放，无论培养基中是否存在Ca²⁺。W - 7（10⁻⁶ - 10⁻⁴mol/l）和W - 5（10⁻⁵和10⁻⁴，或10⁻⁶mol/l）在含Ca²⁺的培养基中显著降低了卡巴胆碱诱导的胃蛋白酶原分泌（分别为对照组的53 - 71%和63 - 81%，p < 0.05 - 0.01）以及CCK - 8诱导的胃蛋白酶原分泌（分别为对照组的49 - 67%和66 - 76%，p < 0.01）。然而，W - 7对环磷酸腺苷（cAMP）和福斯高林诱导的胃蛋白酶原分泌未显示出显著抑制作用。这些发现表明，由细胞内而非细胞外来源动员到胞质溶胶中的细胞内Ca²⁺升高激活的钙调蛋白信使分支在卡巴胆碱和CCK - 8诱导的胃蛋白酶原分泌中起关键作用。胞质溶胶中cAMP的增加似乎不会引发任何钙调蛋白介导的胃蛋白酶原分泌。
