甘丙肽通过胆碱能神经和胰岛素抑制蛙皮素刺激的胰腺淀粉酶分泌。

Barreto Savio G, Woods Charmaine M, Carati Colin J, Schloithe Ann C, Jaya Surendra R, Toouli James, Saccone Gino T P

Department of General and Digestive Surgery, Flinders Medical Centre and Flinders University, Adelaide, South Australia, Australia.

Am J Physiol Gastrointest Liver Physiol. 2009 Aug;297(2):G333-9. doi: 10.1152/ajpgi.00078.2009. Epub 2009 Jun 4.

Pancreatic exocrine secretion is affected by galanin, but the mechanisms involved are unclear. We aimed to determine the effect and elucidate the mechanism of action of exogenous galanin on basal and stimulated pancreatic amylase secretion in vitro. The effect of galanin on basal-, carbachol-, and caerulein-stimulated amylase secretion from isolated murine pancreatic lobules was measured. Carbachol and caerulein concentration-response relationships were established. Lobules were coincubated with galanin (10(-12) M to 10(-7) M), carbachol (10(-6) M), or caerulein (10(-10) M). Lobules were preincubated with atropine (10(-5) M), tetrodotoxin (10(-5) M), hexamethonium (10(-5) M), or diazoxide (10(-7) M and 10(-4) M) for 30 min followed by incubation with caerulein (10(-10) M) alone or combined with galanin (10(-12) M). Amylase secretion was expressed as percent of total lobular amylase. Immunohistochemical studies used the antigen retrieval technique and antisera for galanin receptor (GALR) 1, 2, and 3. Carbachol and caerulein stimulated amylase secretion in a concentration-dependent manner with maximal responses of two- and 1.7-fold over control evoked at 10(-6) M and 10(-10) M, respectively. Galanin (10(-12) M) completely inhibited caerulein-stimulated amylase secretion but had no effect on carbachol-stimulated or basal secretion. Atropine and tetrodotoxin pretreatment abolished the caerulein-stimulated amylase secretion, whereas hexamethonium had no significant effect. Diazoxide significantly reduced caerulein-stimulated amylase secretion by approximately 80%. Galanin did not affect caerulein-stimulated amylase secretion in the presence of hexamethonium or diazoxide. Glucose-stimulated amylase secretion was also inhibited by galanin. Immunohistochemistry revealed islet cells labeled for GALR2. These data suggest that galanin may modulate caerulein-stimulated amylase secretion by acting on cholinergic nerves and/or islet cells possibly via GALR2 to regulate insulin release.

甘丙肽会影响胰腺外分泌，但其中涉及的机制尚不清楚。我们旨在确定外源性甘丙肽对体外基础及刺激状态下胰腺淀粉酶分泌的作用并阐明其作用机制。测定了甘丙肽对分离的小鼠胰腺小叶基础分泌、卡巴胆碱及蛙皮素刺激分泌的淀粉酶的影响。建立了卡巴胆碱和蛙皮素的浓度-反应关系。将小叶与甘丙肽（10⁻¹²M至10⁻⁷M）、卡巴胆碱（10⁻⁶M）或蛙皮素（10⁻¹⁰M）共同孵育。将小叶用阿托品（10⁻⁵M）、河豚毒素（10⁻⁵M）、六甲铵（10⁻⁵M）或二氮嗪（10⁻⁷M和10⁻⁴M）预孵育30分钟，然后单独与蛙皮素（10⁻¹⁰M）或与甘丙肽（10⁻¹²M）联合孵育。淀粉酶分泌以小叶总淀粉酶的百分比表示。免疫组织化学研究采用抗原修复技术及针对甘丙肽受体（GALR）1、2和3的抗血清。卡巴胆碱和蛙皮素以浓度依赖方式刺激淀粉酶分泌，在10⁻⁶M和10⁻¹⁰M时分别比对照引起的最大反应高2倍和1.7倍。甘丙肽（10⁻¹²M）完全抑制蛙皮素刺激的淀粉酶分泌，但对卡巴胆碱刺激的分泌或基础分泌无影响。阿托品和河豚毒素预处理消除了蛙皮素刺激的淀粉酶分泌，而六甲铵无显著影响。二氮嗪使蛙皮素刺激的淀粉酶分泌显著减少约80%。在存在六甲铵或二氮嗪的情况下，甘丙肽不影响蛙皮素刺激的淀粉酶分泌。葡萄糖刺激的淀粉酶分泌也受到甘丙肽的抑制。免疫组织化学显示胰岛细胞有GALR2标记。这些数据表明，甘丙肽可能通过作用于胆碱能神经和/或胰岛细胞，可能经由GALR2来调节胰岛素释放，从而调节蛙皮素刺激的淀粉酶分泌。