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RESEARCH PRODUCT

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

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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-I 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 N-omega-nitro-L-arginine methyl ester (L-NAME) (300 mu M), 1H-(1,2,4) oxadiazolo-(4,3-a) quinoxalin-1-one (ODQ) (10 mu M), apamin (0.1 mu M) or tetrodotoxin (TTX) (I mu M). 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. (c) 2005 Elsevier B.V. All rights reserved.