Li J P, Lee K Y, Chang T M, Chey W Y
Konar Center for Digestive and Liver Diseases, University of Rochester Medical Center, Rochester, NY 14642, USA.
Am J Physiol Gastrointest Liver Physiol. 2001 May;280(5):G890-6. doi: 10.1152/ajpgi.2001.280.5.G890.
We investigated the mechanism of action of methionine enkephalin (MEK) on HCl-stimulated secretin release and pancreatic exocrine secretion. Anesthetized rats with pancreatobiliary cannulas and isolated upper small intestinal loops were perfused intraduodenally with 0.01 N HCl while bile and pancreatic juice were diverted. The effect of intravenous MEK on acid-stimulated secretin release and pancreatic exocrine secretion was then studied with or without coinfusion of naloxone, an anti-somatostatin (SS) serum, or normal rabbit serum. Duodenal acid perfusate, which contains secretin-releasing peptide (SRP) activity, was collected from donor rats with or without pretreatment with MEK, MEK + naloxone, or MEK + anti-SS serum, concentrated by ultrafiltration, and neutralized. The concentrated acid perfusate (CAP), which contains SRP bioactivity, was infused intraduodenally into recipient rats. MEK increased plasma SS concentration and inhibited secretin release and pancreatic fluid and bicarbonate secretion dose-dependently. The inhibition was partially reversed by naloxone and anti-SS serum but not by normal rabbit serum. In recipient rats, CAP increased plasma secretin level and pancreatic secretion. CAP SRP bioactivity decreased when it was collected from MEK-treated donor rats; this was partially reversed by coinfusion with naloxone or anti-SS serum. These results suggest that in the rat, MEK inhibition of acid-stimulated pancreatic secretion and secretin release involves suppression of SRP activity release. Thus the MEK inhibitory effect appears to be mediated in part by endogenous SS.
我们研究了甲硫氨酸脑啡肽（MEK）对盐酸刺激的促胰液素释放及胰腺外分泌的作用机制。对有胰胆管插管和分离的上段小肠袢的麻醉大鼠经十二指肠内灌注0.01 N盐酸，同时引流胆汁和胰液。然后在单独或联合输注纳洛酮、抗生长抑素（SS）血清或正常兔血清的情况下，研究静脉注射MEK对酸刺激的促胰液素释放及胰腺外分泌的影响。从经MEK、MEK +纳洛酮或MEK +抗SS血清预处理或未预处理的供体大鼠收集含有促胰液素释放肽（SRP）活性的十二指肠酸灌注液，经超滤浓缩并中和。将含有SRP生物活性的浓缩酸灌注液（CAP）经十二指肠内注入受体大鼠。MEK剂量依赖性地增加血浆SS浓度，并抑制促胰液素释放以及胰液和碳酸氢盐分泌。纳洛酮和抗SS血清可部分逆转这种抑制作用，而正常兔血清则不能。在受体大鼠中，CAP增加血浆促胰液素水平和胰腺分泌。当从经MEK处理的供体大鼠收集时，CAP的SRP生物活性降低；与纳洛酮或抗SS血清联合输注可部分逆转这种情况。这些结果表明，在大鼠中，MEK对酸刺激的胰腺分泌和促胰液素释放的抑制作用涉及对SRP活性释放的抑制。因此，MEK的抑制作用似乎部分由内源性SS介导。
