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

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.