Extracellular 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 IP₃ signaling pathway shapes unique Ca²⁺ oscillation patterns that allows for distinct cellular responses to different agonists.

与 1,4,5-三磷酸肌醇 (IP ₃ ) 形成相关的细胞外激动剂在许多细胞类型中引发胞质 Ca ²⁺振荡，但尽管有共同的信号通路，但观察到不同的激动剂特异性 Ca ²⁺尖峰模式。使用 qPCR，我们显示大鼠肝细胞表达多种嘌呤能 P2Y 和 P2X 受体 (R)。通过 P2Y1R 起作用的 ADP 引起狭窄的 Ca ²⁺振荡，而通过 P2Y2R 起作用的 UTP 引起广泛的 Ca ²⁺振荡，观察到 ATP 的复合模式。P2XR 在生理激动剂水平上不起作用。离散 Ca ²⁺特征反映了蛋白激酶 C (PKC) 的不同效应，它选择性地改变了 Ca ²⁺尖峰的下降阶段。PKC 的负反馈以需要细胞外 Ca ²⁺的方式限制 P2Y1R 诱导的 Ca ²⁺尖峰的持续时间。相比之下，P2Y2R 对 PKC 负反馈具有抵抗力。因此，分叉的 IP ₃信号通路的 PKC 支路形成独特的 Ca ²⁺振荡模式，允许对不同激动剂的不同细胞反应。