Metabolism and inactivation of gastrin releasing peptide by endopeptidase-24.11 in the dog.

N W Bunnett, A J Turner, H T Debas
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引用次数: 5

Abstract

The purpose of this investigation was to examine the metabolism and inactivation of gastrin releasing peptide 10 (GRP10) by endopeptidase-24.11 prepared from the stomach wall. GRP10 was metabolized in vitro by gastric endopeptidase-24.11. The metabolites were purified by high-pressure liquid chromatography and identified as (1-8) GRP10 and (9-10) GRP10 by amino acid analysis, indicating hydrolysis of the His8-Leu9 bond. The intravenous administration of GRP10 to conscious dogs stimulated gastrin release, gastric acid secretion, pancreatic protein secretion and pancreatic bicarbonate secretion. Incubation of GRP10 with endopeptidase-24.11 significantly diminished the biological activity of the digests compared to control digests containing heat-inactivated enzyme. This effect was abolished by the enzyme inhibitor phosphoramidon. It is concluded that endopeptidase-24.11 from the stomach metabolizes and inactivates GRP10.

内肽酶-24.11对犬胃泌素释放肽代谢及失活的影响。
本研究的目的是研究由胃壁制备的内肽酶-24.11对胃泌素释放肽10 (GRP10)的代谢和失活的影响。GRP10通过胃内肽酶-24.11体外代谢。代谢产物经高压液相色谱纯化,氨基酸分析鉴定为(1-8)GRP10和(9-10)GRP10,表明His8-Leu9键被水解。清醒犬静脉注射GRP10刺激胃泌素释放、胃酸分泌、胰腺蛋白分泌和胰腺碳酸氢盐分泌。与含有热灭活酶的对照酶相比,GRP10与内肽酶-24.11孵育显著降低了酶的生物活性。这种作用被酶抑制剂磷酰胺所消除。由此可见,胃内肽酶-24.11可代谢GRP10并使其失活。
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