![]() Intracellular ATP is primarily utilized to drive energy-dependent processes, such as active transport ( Ataullakhanov and Vitvitsky, 2002). Among the nucleotides, adenosine 5′-triphosphate (ATP) is found in prokaryotes, plants and animals, where it is important for both intracellular and extracellular cell functions. This study provides new insights into the interactions among individual P2 receptors in producing an ensemble response to extracellular ATP.Įxtracellular nucleotides, signaling via P2 receptors, participate in a wide range of biological processes, including neurotransmission, exocrine and endocrine secretion, immune responses, inflammation, pain, and platelet aggregation ( Burnstock and Knight, 2004 Orriss et al., 2012). P2Y4 or P2X5) exerts an inhibitory effect. Interestingly, to describe responses at intermediate ATP concentrations, we had to assume that a receptor with a K 1∕2 in that range (e.g. Fitting the experimental data with a combination of Hill equations from individual receptors revealed that P2Y1 and P2X7 mediated the rise in i at very low and high ATP concentrations, respectively. Dependence of the calcium response on ATP concentration exhibited a complex pattern that was not explained by the simple addition of individual receptor responses. Elevations in the concentration of cytosolic free calcium ( i) were monitored by confocal microscopy. Murine osteoblastic cells (MC3T3-E1 cells) were loaded with fluo-4 and stimulated with varying concentrations of extracellular ATP. Next, we examined responses induced by an ensemble of endogenously expressed P2 receptors. To characterize individual P2 receptors, we extracted data from published studies of overexpressed human and rodent (rat and mouse) receptors and fit their dependencies on ATP concentration using the Hill equation. In the current study, we investigated complex interactions within the P2 receptor network using mathematical modeling. It is known that multiple P2 receptors are expressed on osteoblasts (P2X2,5,6,7 and P2Y1,2,4,6). 5Faculty of Dentistry, McGill University, Montreal, QC, CanadaĮxtracellular ATP acts on the P2X family of ligand-gated ion channels and several members of the P2Y family of G protein-coupled receptors to mediate intercellular communication among many cell types including bone-forming osteoblasts. ![]() 4Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, and Bone and Joint Institute, University of Western Ontario, London, ON, Canada.3Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada.2Shriners Hospital for Children-Canada, Montreal, QC, Canada.1Department of Physics, McGill University, Montreal, QC, Canada.
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