Inhibitory influence of chromogranin A N-terminal fragment (vasostatin-1) on the spontaneous contractions of rat proximal colon

Antonella Amato, Angelo Corti, Rosa Serio, Flavia Mulè

Research output: Contribution to journalArticlepeer-review

Abstract

Very little is known about the role played by CGA and its fragments in the gastrointestinal physiology. We have studied the role of CGA N-terminal fragments in the regulation of intestinal smooth muscle contractility by measuring the influence of recombinant CGA 1-78 (VS-1) and synthetic CGA 7-57 peptides on the spontaneous mechanical activity of rat proximal colon in vitro. The mechanical activity was recorded as changes in the intraluminal pressure. VS-1 (0.1-30 nM) and CGA 7-57 (10-300 nM) produced concentration-dependent inhibitory effects, characterized by a progressive decrease in the mean amplitude of circular muscle spontaneous contractions, without affecting the resting tone. The response to VS-1 was antagonised by anti-CGA monoclonal antibodies (mAb5A8, B4E11, 7D1 or 4D5) but not by an irrelevant antibody, indicating that the effect was specific. The inhibitory responses to VS-1 and to CGA 7-57 were significantly reduced by pre-treatment of the preparations with Nω-nitro-l-arginine methyl ester (l-NAME) (300 μM), 1H-(1,2,4) oxadiazolo-(4,3-a) quinoxalin-1-one (ODQ) (10 μM), apamin (0.1 μM) or tetrodotoxin (TTX) (1 μM). The results suggest that VS-1 plays an inhibitory modulatory role on spontaneous contractions rat colon circular muscle, through mechanisms involving in part neural release of nitric oxide.

Original languageEnglish
Pages (from-to)42-47
Number of pages6
JournalRegulatory Peptides
Volume130
Issue number1-2
DOIs
Publication statusPublished - Aug 15 2005

Keywords

  • CGA-derived peptides
  • Chromogranin A
  • Intestinal smooth muscle
  • Nitric oxide
  • Vasostatin-1

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology
  • Neuroscience(all)

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