Owyang C, May D, Louie D S
Gastroenterology. 1986 Sep;91(3):637-43. doi: 10.1016/0016-5085(86)90633-5.
We have recently demonstrated that intraduodenal perfusion of trypsin inhibits phenylalanine-stimulated pancreatic enzyme secretion by suppression of release of cholecystokinin (CCK). It is not known whether trypsin in the duodenum inhibits pancreatic secretion stimulated by a cholinergic mechanism. To investigate this question gastrointestinal intubation and perfusion were performed in 12 healthy subjects. Volume and osmoreceptors in the duodenum, which are known to elicit pancreatic secretion through cholinergic pathways, were stimulated by infusing increasing volumes (1.0, 2.5, and 5.0 ml/min) of normal saline or increasing osmolality (300, 400, 500 mosmol) of NaCl solution. Increasing the rates of intraduodenal perfusion of normal saline or increasing the osmolality of the duodenal perfusates caused a dose-related increase in pancreatic trypsin and chymotrypsin outputs without affecting basal plasma CCK levels (0.9 +/- 0.1 pM). The volume- or osmolality-stimulated pancreatic secretions were abolished by atropine, but not by intraduodenal perfusion of trypsin. In contrast, intraduodenal perfusion of phenylalanine (10 mM) produced a significant increase in plasma CCK levels (6.7 +/- 0.8 pM) and a three- to fourfold increase in pancreatic enzyme outputs. Perfusion of the duodenum with bovine trypsin (1 g/L) reduced the plasma CCK levels to basal values and significantly attenuated the phenylalanine-stimulated enzyme secretion to 63% +/- 4% of control. Simultaneous administration of atropine and intraduodenal perfusion of trypsin completely abolished the pancreatic enzyme response to phenylalanine stimulation. These studies indicate that the intestinal phase of human pancreatic enzyme secretion is under both hormonal and neural control. Intraduodenal trypsin inhibits only pancreatic secretion mediated by CCK release, and not that mediated by cholinergic mechanisms. These observations suggest that feedback regulation of pancreatic enzyme secretion is stimulus specific.
我们最近证实，十二指肠内灌注胰蛋白酶可通过抑制胆囊收缩素（CCK）的释放来抑制苯丙氨酸刺激的胰腺酶分泌。目前尚不清楚十二指肠内的胰蛋白酶是否会抑制由胆碱能机制刺激的胰腺分泌。为了研究这个问题，我们对12名健康受试者进行了胃肠插管和灌注。通过输注递增体积（1.0、2.5和5.0毫升/分钟）的生理盐水或递增渗透压（300、400、500毫渗量）的氯化钠溶液来刺激十二指肠中的容量和渗透压感受器，已知这些感受器可通过胆碱能途径引发胰腺分泌。增加十二指肠内生理盐水的灌注速率或增加十二指肠灌注液的渗透压会导致胰腺胰蛋白酶和糜蛋白酶分泌量呈剂量相关增加，而不影响基础血浆CCK水平（0.9±0.1皮摩尔）。容量或渗透压刺激引起的胰腺分泌可被阿托品消除，但不能被十二指肠内灌注胰蛋白酶消除。相比之下，十二指肠内灌注苯丙氨酸（10毫摩尔）可使血浆CCK水平显著升高（6.7±0.8皮摩尔），胰腺酶分泌量增加三到四倍。用牛胰蛋白酶（1克/升）灌注十二指肠可使血浆CCK水平降至基础值，并使苯丙氨酸刺激的酶分泌显著减弱至对照值的63%±4%。同时给予阿托品和十二指肠内灌注胰蛋白酶可完全消除胰腺酶对苯丙氨酸刺激的反应。这些研究表明，人胰腺酶分泌的肠期受激素和神经双重控制。十二指肠内的胰蛋白酶仅抑制由CCK释放介导的胰腺分泌，而不抑制由胆碱能机制介导的分泌。这些观察结果表明，胰腺酶分泌的反馈调节具有刺激特异性。
