Abstract:
The T2R family of bitter taste receptors is expressed in enteroendocrine cells of the gastrointestinal tract where they modulate gastric emptying and satiety. This functionality is mediated by calcium signalling leading to the secretion of hormones involved in nutrient sensing, satiety and the control of gastrointestinal motility. In this work we present a mathematical model of calcium signalling in the HuTu 80 model of enteroendocrine cells. The model is based upon a previous description of calcium dynamics initiated by Gprotein coupled receptors. It incorporates the kinetics of ligand binding; G-protein activation, inactivation and recycling; inositol triphosphate (IP3) production and degradation; calcium release from the endoplasmic reticulum and describes intracellular calcium dynamics upon exposure to bitter ligands. Model parameters were determined by fitting predictions to fluorescent measurements of intracellular calcium concentrations in HuTu 80 cells in response to chlorhexidine stimulation. Experimentally measured calcium dynamics exhibited a slow rise time and sustained response. The rise time and steady state response were dose dependent. The model was able to reproduce these features when ligand-receptor affinity and the activation/inactivation rates of the G-protein were low.