| Full text | |
| 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]
Total Authors: 6
|
| 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
Total Affiliations: 2
|
| 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 |