6533b7d7fe1ef96bd1267a83

RESEARCH PRODUCT

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

Flavia MulèRosa SerioAntonella Amato

subject

endocrine systemmedicine.medical_specialtyPhysiologyMuscle RelaxationClinical BiochemistryBiologyIn Vitro TechniquesApaminInhibitory postsynaptic potentialBiochemistrySettore BIO/09 - FisiologiaNitric oxideContractilityGastric relaxationCellular and Molecular Neurosciencechemistry.chemical_compoundMiceEndocrinologyInternal medicinemedicineAnimalsGastrointestinal tractCGA-derived peptideDose-Response Relationship DrugStomachChromogranin ANitric oxideMuscle SmoothMolecular biologyIn vitroPeptide FragmentsRecombinant ProteinsMice Inbred C57BLEndocrinologychemistryTetrodotoxinbiology.proteinVasostatinChromogranin ACalreticulin

description

Abstract 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.

10.1016/j.regpep.2006.10.010https://pubmed.ncbi.nlm.nih.gov/17126925