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• W2012803933 abstract "β-Carbolines (including harmane and pinoline) stimulate insulin secretion by a mechanism that may involve interaction with imidazoline I3-receptors but which also appears to be mediated by actions that are additional to imidazoline receptor agonism. Using the MIN6 β-cell line, we now show that both the imidazoline I3-receptor agonist, efaroxan, and the β-carboline, harmane, directly elevate cytosolic Ca2+ and increase insulin secretion but that these responses display different characteristics. In the case of efaroxan, the increase in cytosolic Ca2+ was readily reversible, whereas, with harmane, the effect persisted beyond removal of the agonist and resulted in the development of a repetitive train of Ca2+-oscillations whose frequency, but not amplitude, was concentration-dependent. Initiation of the Ca2+-oscillations by harmane was independent of extracellular calcium but was sensitive to both dantrolene and high levels (20 mM) of caffeine, suggesting the involvement of ryanodine receptor-gated Ca2+-release. The expression of ryanodine receptor-1 and ryanodine receptor-2 mRNA in MIN6 cells was confirmed using reverse transcription-polymerase chain reaction (RT-PCR) and, since low concentrations of caffeine (1 mM) or thimerosal (10 μM) stimulated increases in [Ca2+]i, we conclude that ryanodine receptors are functional in these cells. Furthermore, the increase in insulin secretion induced by harmane was attenuated by dantrolene, consistent with the involvement of ryanodine receptors in mediating this response. By contrast, the smaller insulin secretory response to efaroxan was unaffected by dantrolene. Harmane-evoked changes in cytosolic Ca2+ were maintained by nifedipine-sensitive Ca2+-influx, suggesting the involvement of L-type voltage-gated Ca2+-channels. Taken together, these data imply that harmane may interact with ryanodine receptors to generate sustained Ca2+-oscillations in pancreatic β-cells and that this effect contributes to the insulin secretory response." @default.
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• W2012803933 date "2004-10-01" @default.
• W2012803933 modified "2023-09-25" @default.
• W2012803933 title "The putative imidazoline receptor agonist, harmane, promotes intracellular calcium mobilisation in pancreatic β-cells" @default.
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• W2012803933 doi "https://doi.org/10.1016/j.ejphar.2004.08.018" @default.
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