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

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Abstract

Very little is known about the role played by CGA and its fragments in the gastrointestinal physiology. We have studied the role of CGAN-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 wasrecorded as changes in the intraluminal pressure. VS-1 (0.1–30 nM) and CGA 7–57 (10–300 nM) produced concentration-dependentinhibitory effects, characterized by a progressive decrease in the mean amplitude of circular muscle spontaneous contractions, withoutaffecting the resting tone. The response to VS-1 was antagonised by anti-CGA monoclonal antibodies (mAb5A8, B4E11, 7D1 or 4D5) butnot by an irrelevant antibody, indicating that the effect was specific. The inhibitory responses to VS-1 and to CGA 7–57 were significantlyreduced by pre-treatment of the preparations with Nx-nitro-l-arginine methyl ester (l-NAME) (300 AM), 1H-(1,2,4) oxadiazolo-(4,3-a)quinoxalin-1-one (ODQ) (10 AM), apamin (0.1 AM) or tetrodotoxin (TTX) (1 AM). The results suggest that VS-1 plays an inhibitorymodulatory role on spontaneous contractions rat colon circular muscle, through mechanisms involving in part neural release of nitric oxide.
Lingua originaleEnglish
pagine (da-a)42-47
Numero di pagine6
RivistaRegulatory Peptides
Volume130
Stato di pubblicazionePublished - 2005

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology
  • Endocrinology
  • Clinical Biochemistry
  • Cellular and Molecular Neuroscience

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