Ballantyne G H, Zdon M J, Schafer D E, Fratesi G R, Roberts J R, Tyshkov M, Modlin I M
Ann Surg. 1986 Nov;204(5):559-65. doi: 10.1097/00000658-198611000-00009.
The cellular mechanisms by which pepsinogen (PNG) secretion is controlled are not understood. The aim of this study was to explore whether modulation of PNG secretion is mediated by cAMP or calcium-calmodulin (C-C). PNG secretion in isolated rabbit gastric fundic glands (IGG) was tested, using agents believed to act via cAMP or C-C. IGG were stimulated for 30 minutes with histamine (H) 10(-5) M, isoproterenol (I) 10(-5) M, carbachol (C) 10(-5) M, cholecystokinin-octapeptide (CCK-8) 10(-7) M, forskolin (F) 10(-5) M, 8 bromo-cAMP (8B) 10(-3) M, and A23187 (A) 10(-6) M. PNG levels were determined by spectrophotometric assay of hemoglobin digestion products. PNG amounts secreted were (mean per cent above basal levels of total IGG PNG units +/- SEM): H, -0.02 +/- 0.30%; I, 3.5 +/- 0.9%; C, 5.1 +/- 2.2%; CCK-8, 5.3 +/- 1.5%; F, 10.6 +/- 3.8%; 8B, 13.8 +/- 4.5%; A, 2.1 +/- 1.1%. All secretagogues except H stimulated PNG release significantly above basal levels (p less than 0.05). A primary histaminergic mechanism for pepsinogen secretion is unlikely. Since two other adenylate cyclase activators, isoproterenol and forskolin and the 3':5'-cyclic adenosine monophosphate analog 8-bromo cAMP stimulated pepsinogen secretion, cAMP-dependence is probable. Since carbachol, CCK-8, and A23187, which are believed to act via calcium-calmodulin, also stimulated pepsinogen secretion, this system, too, presumably plays a substantial role. Thus the data support a dual 3':5'-cyclic adenosine monophosphate/calcium-calmodulin modulation of pepsinogen secretion.
目前尚不清楚胃蛋白酶原（PNG）分泌的细胞调控机制。本研究旨在探讨PNG分泌的调节是否由环磷酸腺苷（cAMP）或钙 - 钙调蛋白（C - C）介导。使用被认为通过cAMP或C - C起作用的试剂，对分离的兔胃底腺（IGG）中的PNG分泌进行检测。用10(-5)M组胺（H）、10(-5)M异丙肾上腺素（I）、10(-5)M卡巴胆碱（C）、10(-7)M胆囊收缩素八肽（CCK - 8）、10(-5)M福斯可林（F）、10(-3)M 8 - 溴 - cAMP（8B）和10(-6)M A23187（A）刺激IGG 30分钟。通过对血红蛋白消化产物的分光光度测定来确定PNG水平。分泌的PNG量为（相对于总IGG PNG单位基础水平的平均百分比±标准误）：H，-0.02±0.30%；I，3.5±0.9%；C，5.1±2.2%；CCK - 8，5.3±1.5%；F，10.6±3.8%；8B，13.8±4.5%；A，2.1±1.1%。除H外，所有促分泌剂均显著刺激PNG释放高于基础水平（p小于0.05）。胃蛋白酶原分泌不太可能存在主要的组胺能机制。由于另外两种腺苷酸环化酶激活剂异丙肾上腺素和福斯可林以及3':5'-环磷酸腺苷类似物8 - 溴 - cAMP刺激了胃蛋白酶原分泌，因此很可能存在cAMP依赖性。由于据信通过钙 - 钙调蛋白起作用的卡巴胆碱、CCK - 8和A23187也刺激了胃蛋白酶原分泌，所以该系统可能也起着重要作用。因此，数据支持3':5'-环磷酸腺苷/钙 - 钙调蛋白对胃蛋白酶原分泌的双重调节。
