Relaxation induced by N-terminal fragments of chromogranin A in mouse gastric preparations.

A definitive role for chromogranin A (CGA)-derived fragments in the control of the gastrointestinal smooth muscle contractility has not beenyet established. The purpose of the present study was to evaluate, in vitro, the effects of the recombinant vasostatin 1–78 (VS-1), CGA 7–57 andCGA 47–66 on the mouse gastric mechanical activity, recording the changes of intraluminal pressure. VS-1, CGA 7–57 and CGA 47–66produced concentration-dependent relaxations. Mouse anti-vasostatin-1 monoclonal antibody 5A8, recognising the region 53–57, abolished therelaxation induced by VS-1, indicating the specificity of the effect. The relaxation was significantly reduced by tetrodotoxin (TTX), blocker ofneuronal voltage-dependent Na+ channels, L-NAME, inhibitor of nitric oxide (NO) synthase, or apamin, blocker of small conductance Ca2+-dependent K+ channels. The joint application of TTX and L-NAME did not show any additive effects, whereas TTX plus apamin abolished theVS-1 response. The results suggest that the N-terminal CGA-derived peptides are able to relax mouse gastric muscle and, therefore, they point outan inhibitory role of vasostatin I in the gastrointestinal tract. The relaxation is mediated in part by neural mechanisms through NO production andin part by non-neural mechanisms involving the opening of small conductance Ca2+-dependent K+ channels.