Signal transduction via P2-purinergic receptors for extracellular ATP and other nucleotides.

Extracellular ATP, at micromolar concentrations, induces significant functional changes in a wide variety of cells and tissues. ATP can be released from the cytosol of damaged cells or from exocytotic vesicles and/or granules contained in many types of secretory cells. There are also efficient extracellular mechanisms for the rapid metabolism of released nucleotides by ecto-ATPases and 5'-nucleotidases.

Dissociation of the pore-forming and phospholipase D activities stimulated via P2z purinergic receptors in BAC1.2F5 macrophages. Product inhibition of phospholipase D enzyme activity.

We have previously reported that the occupancy of P2z purinergic receptors in BAC1.2F5 macrophages stimulates both the formation of nonselective membrane pores/channels and a novel phospholipase D (PLD) activity. In the present study, the relationship between these two P2z receptor-mediated responses was investigated.

Expression of the pore-forming P2Z purinoreceptor in Xenopus oocytes injected with poly(A)+ RNA from murine macrophages.

Extracellular ATP activates two distinct types of P2 purinoreceptor-mediated signaling pathways in macrophages, 1) the rapid formation of nonselective pores/channels in the plasma membrane and 2) a guanine nucleotide-binding protein-dependent stimulation of phosphotidylinositol-specific phospholipase C, with subsequent mobilization of intracellular Ca2+. Several studies have suggested that the pore-forming, or P2z, purinoreceptor may be involved in the cytolytic effects of ATP on macrophages and other cell types. We have identified 3'-O-(4-benzoyl)benzoyl-ATP (BzATP) and UTP as selective agonists for the P2z purinoreceptor and Ca(2+)-mobilizing nucleotide receptor, respectively, in BAC1.

A novel pathway for the activation of phospholipase D by P2z purinergic receptors in BAC1.2F5 macrophages.

Macrophages express two distinct types of nucleotide (P2 purinergic) receptors for extracellular ATP: one type induces a Ca(2+)-mobilizing response via the activation of phosphatidylinositol-phospholipase C (PI-PLC) while the second type induces the rapid formation of nonselective pores which are permeated by ions and small (< 1 kDa) organic molecules. We have confirmed the presence of these two ATP receptor types in the BAC1.2F5 murine macrophage cell line and have identified 3'-O-(4-benzoyl)benzoyl-ATP (BzATP) as a selective and potent agonist for the so-called P2z or pore-forming ATP receptor type.