Ca entry through reverse Na+/Ca exchanger in NCI-H716, glucagon-like peptide-1 secreting cells.

Glucagon like peptide-1 (GLP-1) released from enteroendocine L-cells in the intestine has incretin effects due to its ability to amplify glucose-dependent insulin secretion. Promotion of an endogenous release of GLP-1 is one of therapeutic targets for type 2 diabetes mellitus. Although the secretion of GLP-1 in response to nutrient or neural stimuli can be triggered by cytosolic Ca elevation, the stimulus-secretion pathway is not completely understood yet. Therefore, the aim of this study was to investigate the role of reverse Na/Ca exchanger (rNCX) in Ca entry induced by muscarinic stimulation in NCI-H716 cells, a human enteroendocrine GLP-1 secreting cell line. Intracellular Ca was repetitively oscillated by the perfusion of carbamylcholine (CCh), a muscarinic agonist. The oscillation of cytosolic Ca was ceased by substituting extracellular Na with Li+ or NMG+. KB-R7943, a specific rNCX blocker, completely diminished CCh-induced cytosolic Ca oscillation. Type 1 Na/Ca exchanger (NCX) proteins were expressed in NCI-H716 cells. These results suggest that rNCX might play a crucial role in Ca entry induced by cholinergic stimulation in NCI-H716 cells, a GLP-1 secreting cell line.