Receptor-specific Ca Oscillation Patterns Mediated by Differential Regulation of P2Y Purinergic Receptors in Rat Hepatocytes

Overview

Journal iScience

Publisher Cell Press

Date 2021 Oct 14

PMID 34646983

Citations 1

Authors

Juliana C Correa-Velloso

Paula J Bartlett

Robert Brumer

Lawrence D Gaspers

Henning Ulrich

Andrew P Thomas

Affiliations

Soon will be listed here.

Abstract

Extracellular agonists linked to inositol-1,4,5-trisphosphate (IP) formation elicit cytosolic Ca oscillations in many cell types, but despite a common signaling pathway, distinct agonist-specific Ca 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 Ca oscillations, whereas UTP acting through P2Y2R elicits broad Ca oscillations, with composite patterns observed for ATP. P2XRs do not play a role at physiological agonist levels. The discrete Ca signatures reflect differential effects of protein kinase C (PKC), which selectively modifies the falling phase of the Ca spikes. Negative feedback by PKC limits the duration of P2Y1R-induced Ca spikes in a manner that requires extracellular Ca. By contrast, P2Y2R is resistant to PKC negative feedback. Thus, the PKC leg of the bifurcated IP signaling pathway shapes unique Ca oscillation patterns that allows for distinct cellular responses to different agonists.

Citing Articles

Purinergic signaling in liver disease: calcium signaling and induction of inflammation.

Ulrich H, Glaser T, Thomas A Purinergic Signal. 2024; .

PMID: 39320433 DOI: 10.1007/s11302-024-10044-9.

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