Extracellular NAD+ Is an Agonist of the Human P2Y11 Purinergic Receptor in Human Granulocytes

Iliana Moreschi,Santina Bruzzone,Robert A Nicholas,Floriana Fruscione,Laura Sturla,Federica Benvenuto,Cesare Usai,Sabine Meis,Matthias U Kassack,Elena Zocchi,Antonio De Flora

doi:10.1016/s0021-9258(19)84054-1

Abstract

Extracellular NAD+ Is an Agonist of the Human P2Y11 Purinergic Receptor in Human Granulocytes

Highlights

CAMP, (ii) activation of protein kinase A, (iii) stimulation of ADP-ribosyl cyclase and overproduction of cyclic ADP-ribose, a universal Ca2؉ mobilizer, and (iv) influx of extracellular Ca2؉
We demonstrate that exposure of granulocytes to millimolar rather than to micromolar NADe؉ generates both inositol 1,4,5-trisphosphate (IP3) and cAMP, with a two-step elevation of intracellular calcium levels ([Ca2؉]i): a rapid, IP3mediated Ca2؉ release, followed by a sustained influx of extracellular Ca2؉ mediated by cyclic ADP-ribose (cADPR)
Given that (i) NADϩ is a nucleotide and (ii) NADeϩ-induced intracellular increases of IP3, cAMP, cADPR, and [Ca2ϩ]i were abrogated by suramin, a relatively non-selective inhibitor of P2Y receptors, we focused on the possibility that the signaling activities promoted by NADeϩ were the result of activation of a G protein-coupled P2Y receptor

Summary

Introduction

CAMP, (ii) activation of protein kinase A, (iii) stimulation of ADP-ribosyl cyclase and overproduction of cyclic ADP-ribose (cADPR), a universal Ca2؉ mobilizer, and (iv) influx of extracellular Ca2؉. To address the type of receptors that mediate the NADeϩ-induced Ca2ϩ responses in human granulocytes, intact cells were preincubated with suramin, a widely used antagonist of both G protein-coupled P2Y

Results

Conclusion