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标题：Receptor-specific Ca 2+ oscillation patterns mediated by differential regulation of P2Y purinergic receptors in rat hepatocytes
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作者：Juliana C. Corrêa-Velloso ; Paula J. Bartlett ; Robert Brumer 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：10
页码：1-23
DOI：10.1016/j.isci.2021.103139
语种：English
出版社：Elsevier
摘要：SummaryExtracellular agonists linked to inositol-1,4,5-trisphosphate (IP3) formation elicit cytosolic Ca2+oscillations in many cell types, but despite a common signaling pathway, distinct agonist-specific Ca2+spike patterns are observed. Using qPCR, we show that rat hepatocytes express multiple purinergic P2Y and P2X receptors (R). ADP acting through P2Y1R elicits narrow Ca2+oscillations, whereas UTP acting through P2Y2R elicits broad Ca2+oscillations, with composite patterns observed for ATP. P2XRs do not play a role at physiological agonist levels. The discrete Ca2+signatures reflect differential effects of protein kinase C (PKC), which selectively modifies the falling phase of the Ca2+spikes. Negative feedback by PKC limits the duration of P2Y1R-induced Ca2+spikes in a manner that requires extracellular Ca2+. By contrast, P2Y2R is resistant to PKC negative feedback. Thus, the PKC leg of the bifurcated IP3signaling pathway shapes unique Ca2+oscillation patterns that allows for distinct cellular responses to different agonists.Graphical abstractDisplay OmittedHighlights•Distinct stereotypic Ca2+oscillations are elicited by P2Y1 and P2Y2 receptors•P2X receptors do not contribute to the generation of Ca2+oscillations•Agonist-specific Ca2+spike shapes reflect discrete modes of PKC negative feedback•Bifurcation of IP3/PKC signaling yields unique Ca2+oscillation signaturesBiological sciences; Cell biology; Cellular physiology; Functional aspects of cell biology