科研之友
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摘要
Background: Depletion of the GPCR T1R1/T1R3 increased calcium and ERK1/2 signaling by carbachol. Results: T1R3 depletion or reducing amino acids overnight increased M3 muscarinic receptor expression and altered calcium responses. Conclusion: M3 receptor expression in cells is up-regulated by reduced amino acid availability. Significance: The M3 muscarinic receptor is a potential therapeutic target in cells with impaired amino acid sensitivity. We have shown recently that the class C G protein-coupled receptor T1R1/T1R3 taste receptor complex is an early amino acid sensor in MIN6 pancreatic cells. Amino acids are unable to activate ERK1/2 in cells in which T1R3 has been depleted. The muscarinic receptor agonist carbachol activated ERK1/2 better in T1R3-depleted cells than in control cells. Ligands that activate certain G protein-coupled receptors in pancreatic cells potentiate glucose-stimulated insulin secretion. Among these is the M3 muscarinic acetylcholine receptor, the major muscarinic receptor in cells. We found that expression of M3 receptors increased in T1R3-depleted MIN6 cells and that calcium responses were altered. To determine whether these changes were related to impaired amino acid signaling, we compared responses in cells exposed to reduced amino acid concentrations. M3 receptor expression was increased, and some, but not all, changes in calcium signaling were mimicked. These findings suggest that M3 acetylcholine receptors are increased in cells as a mechanism to compensate for amino acid deficiency.
- 出版日期2014-5-16
