Receptor-specific Ca2+ oscillation patterns mediated by differential regulation of P2Y purinergic receptors in rat hepatocytes

Author(s)

Correa-Velloso, Juliana C. ^[1] ; Bartlett, Paula J. ^[1] ; Brumer, Robert ^[1] ; Gaspers, Lawrence D. ^[1] ; Ulrich, Henning ^[2] ; Thomas, Andrew P. ^[1]

Affiliation

^[1] Rutgers State Univ, New Jersey Med Sch, Dept Pharmacol Physiol & Neurosci, Newark, NJ 07103 - USA

^[2] Univ Sao Paulo, Inst Chem, Dept Biochem, Sao Paulo - Brazil

• Document type: Journal article
• Source: ISCIENCE; v. 24, n. 10 OCT 22 2021.
• Web of Science Citations: 0

Abstract

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. (AU)

• FAPESP's process: 18/07366-4 - Purine and kinin receptors as targets of study and therapeutic interventions in neurological diseases
• Grantee: Alexander Henning Ulrich
• Support Opportunities: Research Projects - Thematic Grants