Signaling pathways downstream of P2 receptors in human neutrophils.

Purinergic Signalling
John MeshkiSatya P Kunapuli

Abstract

Extracellular nucleotides stimulate human neutrophils by activating the purinergic P2Y(2) receptor. However, it is not completely understood which types of G proteins are activated downstream of this P2 receptor subtype. We investigated the G-protein coupling to P2Y(2) receptors and several subsequent signaling events. Treatment of neutrophils with pertussis toxin (PTX), a Gi protein inhibitor, caused only approximately 75% loss of nucleotide-induced Ca(2+) mobilization indicating that nucleotides cause Ca(2+) mobilization both through Gi-dependent and Gi-independent pathways. However, the PLC inhibitor U73122 almost completely inhibited Ca(2+) mobilization in both nucleotide- and fMLP-stimulated neutrophils, strongly supporting the view that both the PTX-sensitive and the PTX-insensitive mechanism of Ca(2+) increase require activation of PLC. We investigated the dependence of ERK phosphorylation on the Gi pathway. Treatment of neutrophils with PTX caused almost complete inhibition of ERK phosphorylation in nucleotide or fMLP activated neutrophils. U73122 caused inhibition of nucleotide- or fMLP-stimulated ERK phosphorylation, suggesting that although pertussis toxin-insensitive pathways cause measurable Ca(2+) mobilization, th...Continue Reading

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Citations

Dec 3, 2013·Apoptosis : an International Journal on Programmed Cell Death·Boris K PliyevValery G Savchenko
Jan 7, 2016·Journal of Pineal Research·Luis Henrique Souza-TeodoroZ S Ferreira
Oct 28, 2008·Clinical Nutrition : Official Journal of the European Society of Parenteral and Enteral Nutrition·Michelle W J VersleijenGeert J A Wanten
Aug 26, 2011·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Celia CarrilloSara R Alonso-Torre
Apr 25, 2015·Molecular Systems Biology·Sean R CollinsTobias Meyer
Oct 26, 2012·The Journal of Pharmacology and Experimental Therapeutics·Elisabetta LiveraniSatya P Kunapuli

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