Experimental Physiology
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Quarterly Journal of Experimental Physiology 74.5 pp 727-734
© The Physiological Society 1989
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METABOLISM AND INACTIVATION OF GASTRIN RELEASING PEPTIDE BY ENDOPEPTIDASE-24.11 IN THE DOG

N. W. Bunnett 1, A. J. Turner 2, and H. T. Debas 1

1 Department of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA
2 MRC Membrane Peptidase Research Group, Department of Biochemistry, University of Leeds, Leeds LS2 9JT

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.

Submitted on December 24, 1988
Accepted on February 23, 1989






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Copyright © 1989 by the The Physiological Society.