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 been yet 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 and CGA 47-66 on the mouse gastric mechanical activity, recording the changes of intraluminal pressure. VS-1, CGA 7-57 and CGA 47-66 produced concentration-dependent relaxations. Mouse anti-vasostatin-1 monoclonal antibody 5A8, recognising the region 53-57, abolished the relaxation induced by VS-1, indicating the specificity of the effect. The relaxation was significantly reduced by tetrodotoxin (TTX), blocker of neuronal voltage-dependent Na(+) channels, l-NAME, inhibitor of nitric oxide (NO) synthase, or apamin, blocker of small conductance Ca(2+)-dependent K(+) channels. The joint application of TTX and l-NAME did not show any additive effects, whereas TTX plus apamin abolished the VS-1 response. The results suggest that the N-terminal CGA-derived peptides are able to relax mouse gastric muscle and, therefore, they point out an inhibitory role of vasostatin I in the gastrointestinal tract. The relaxation is mediated in part by neural mechanisms through NO production and in part by non-neural mechanisms involving the opening of small conductance Ca(2+)-dependent K(+) channels.
Amato
Antonella
A
Dipartimento di Biologia cellulare e dello Sviluppo, Università di Palermo, 90128 Palermo, Italy.
Serio
Rosa
R
Mulè
Flavia
F
D000818:Animals; D037282:Calreticulin / Q000235:genetics / Q000494:pharmacology; D053379:Chromogranin A / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects; D010446:Peptide Fragments / Q000235:genetics / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013270:Stomach / Q000187:drug effects* / Q000502:physiology
D037282:Calreticulin; D053379:Chromogranin A; D010446:Peptide Fragments; D011994:Recombinant Proteins; C121986:vasostatin