Antibody Panel to Purinergic Receptors - Product Review 06

Introduction

Studies of extracellular ATP release have revealed its importance for many autocrine or paracrine regulatory processes in nearly all body tissues. Several cell membrane receptors, which preferentially bind extracellular nucleotides, and their analogs have been identified. These receptors are collectively known as nucleotide receptors or "purinergic" receptors. For example these receptors play a significant role in regulating ion transport in epithelial tissues through a variety of intracellular signalling pathways. Activation of these receptors is partially dependent on ATP (or UTP) release from cells, often in the setting of cellular damage.

Purinergic receptors are a family of ubiquitous transmembrane receptors comprising of two main classes: those stimulated by adenosine are classified as P1 receptors and those that respond to extracellular nucleotides (i.e. ATP, ADP, UTP and UDP) are known as P2 receptors (see Fig. 1). There are four subtypes within the P1 receptor class: A1, A2a, A2b, and A3. The A2 subtypes are coupled to Gs and stimulate adenylyl cyclase, whereas A1 and A3 are coupled to Go/Gi and inhibit adenylyl cyclase. Membrane-bound P2-receptors mediate the actions of extracellular nucleotides in cell-to-cell signalling. P2X-receptors are ligand-gated ion channels, whereas P2Yreceptors belong to the superfamily of G-protein-coupled receptors (GPCR).

P2X1 is present in smooth muscle as well as in the central and peripheral nervous system. P2X2 is expressed in brain, spinal cord, sensory and autonomic ganglia as well as in neuroendocrine cells. P2X3 is expressed in nociceptive sensory neurons.

So far, the P2Y receptor family is composed of several cloned and functionally defined subtypes. Twelve of them are currently known to be present in human tissues:

The distribution of P2Y1 mRNA is widespread. The receptor plays a crucial role in platelet aggregation and mediates the adenine nucleotide- induced release of NO. P2Y2 transcripts are abundantly distributed. It regulates for example chloride ion fluxes in airway epithelia. The P2Y4-receptor is highly expressed in the placenta. The distribution of the P2Y6-receptor is widespread including heart, blood vessels and brain. P2Y7 is a Receptor for extracellular ATP > UTP and ADP. The activity of this receptor is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system. May be the cardiac P2Y receptor involved in the regulation of cardiac muscle contraction through modulation of L-type calcium currents. Is a receptor for leukotriene B4, a potent chemoattractant involved in inflammation and immumne response. P2Y7 is expressed at highest levels in heart, skeletal muscle and at lower levels in brain and liver. High level of expression in lymphoid tissues. P2Y8 ESTs have been isolated from human normal tonsil and lymph libraries and from human lung and lymphoma cancer libraries. P2Y9 also known as GPR23 ESTs have been isolated from brain and melanocyte/uterus/fetal heart libraries. Northern blot analysis failed to reveal P2Y9 messenger in 16 human organs; however, functional expression was accomplished in 3 distinct systems: transient expression in COS-7 cells, stable expression in 1321N1 and CHO-K1 cells. P2Y10 has been reported to be expressed in lymphoid cells and in monocytes derived from dendritic cells. The P2Y11-receptor may play a role in the differentiation of immunocytes. Expression of P2Y12 has been reported in platelets, spinal cord, and many brain regions. P2Y13 is an Orphan receptor. It seems to be a G(i)-coupled receptor displaying a high affinity for ADP. It might play a role in hematopoiesis and the immune system. Strong expression is observed in spleen and adult brain, lower expression in placenta, lung, liver, spinal cord, thymus, small intestine, uterus, stomach, testis, fetal brain, and adrenal gland. In addition P2Y13 expression was ´clearly detected in lymph node and bone marrow, buut only weakly in peripheral blood mononuclear cells (PBMC) and in peripheral blood leukocytes (PBL). In the brain, it was detected in all brain regions examined. P2Y14 is a receptor for UDP-glucose and other UDP-sugar coupled to G-proteins. Not activated by ATP, ADP, UTP or ATP. Highest expression was detected in the placenta, adipose tissue, stomach and intestine, intermediate levels in the brain, spleen, lung and heart, lowest levels in the kidney.

Fig.1: Schematic view of a G-Protein coupled P2Y receptor and an 'ionotropic' P2X receptor. The physiological ligand for both receptors is ATP and its metabolites. On gating by nucleotide ligand, P2X receptor channels are permeable to Ca2+ and Na+ entering the cell down large chemical gradients and to K+ leaving the cell down its chemical gradient. It is thought that ATP binds in the extracellular domain, although a binding site has not been mapped. In contrast, the structure of P2Y receptors is much like that of other GPCRs.

Fig.1: Schematic view of a G-Protein coupled P2Y receptor and an 'ionotropic' P2X receptor. The physiological ligand for both receptors is ATP and its metabolites. On gating by nucleotide ligand, P2X receptor channels are permeable to Ca2+ and Na+ entering the cell down large chemical gradients and to K+ leaving the cell down its chemical gradient. It is thought that ATP binds in the extracellular domain, although a binding site has not been mapped. In contrast, the structure of P2Y receptors is much like that of other GPCRs.

Antibody Tools for Detection of Purinergic Receptors

Acris Antibodies offers a wide range of antibodies to purinergic receptors. All products provide excellent tools for studying nucleotide receptor function and expression in different tissues.

Picture Gallery

Staining of neurons in human brain using anti P2Y1 polyclonal antibody cat# SP4009

Staining of neurons in human brain using anti P2Y1 polyclonal antibody cat# SP4009

Staining of neutrophils and macrophages in human tonsil using anti P2Y4 polyclonal antibody cat# SP4007P

Staining of neutrophils and macrophages in human tonsil using anti P2Y4 polyclonal antibody cat# SP4007P

Staining of human macrophages using anti P2Y5 antibody cat# SP4556P

Staining of human macrophages using anti P2Y5 antibody cat# SP4556P

Staining of endothelial reticular cells in human thymus using anti P2Y5 antibody cat# SP4555P

Staining of endothelial reticular cells in human thymus using anti P2Y5 antibody cat# SP4555P

Staining of human placenta using anti P2Y6 polyclonal antibody cat# SP4007P

Staining of human placenta using anti P2Y6 polyclonal antibody cat# SP4007P

Staining of human placenta using anti P2Y6 polyclonal antibody cat# SP4011P

Staining of human placenta using anti P2Y6 polyclonal antibody cat# SP4011P

Staining of human placenta using anti P2Y6 polyclonal antibody cat# SP4011P

Staining of human placenta using anti P2Y6 polyclonal antibody cat# SP4011P

Staining of human tonsil using anti P2Y8 polyclonal antibody cat# SP4025P

Staining of human tonsil using anti P2Y8 polyclonal antibody cat# SP4025P

Staining of human melanoma anti P2Y9/GRP23 polyclonal antibody cat# SP4378P

Staining of human melanoma anti P2Y9/GRP23 polyclonal antibody cat# SP4378P

Staining of human spleen using anti P2Y10 polyclonal antibody cat# SP4026P

Staining of human spleen using anti P2Y10 polyclonal antibody cat# SP4026P

Staining of human spleen using anti P2Y10 polyclonal antibody cat# SP4027P

Staining of human spleen using anti P2Y10 polyclonal antibody cat# SP4027P

Staining of dendritic cells using anti P2Y11 polyclonal antibody cat# SP4018P

Staining of dendritic cells using anti P2Y11 polyclonal antibody cat# SP4018P

Staining of dendritic cells using anti P2Y11 polyclonal antibody cat# SP4019P

Staining of dendritic cells using anti P2Y11 polyclonal antibody cat# SP4019P

Staining of Megakaryocytes using anti P2Y12 polyclonal antibody cat# SP4030P

Staining of Megakaryocytes using anti P2Y12 polyclonal antibody cat# SP4030P

Staining of platelets in human blood anti P2Y12 polyclonal antibody cat# SP4442P

Staining of platelets in human blood anti P2Y12 polyclonal antibody cat# SP4442P

Staining of human spleen using anti P2Y13 polyclonal antibody cat# SP4263P

Staining of human spleen using anti P2Y13 polyclonal antibody cat# SP4263P

Staining of human spleen using anti P2Y13 polyclonal antibody cat# SP4265P

Staining of human spleen using anti P2Y13 polyclonal antibody cat# SP4265P

Staining of neurons and glia in human brain using anti P2Y14 polyclonal antibody cat# SP4179P

Staining of neurons and glia in human brain using anti P2Y14 polyclonal antibody cat# SP4179P

Staining of human placenta using anti P2Y14 polyclonal antibody cat# SP4178P

Staining of human placenta using anti P2Y14 polyclonal antibody cat# SP4178P

Staining of human placenta using anti P2Y15 antibody cat# SP4557P

Staining of human placenta using anti P2Y15 antibody cat# SP4557P

Staining of human placenta using anti P2Y15 antibody cat# SP4558P

Staining of human placenta using anti P2Y15 antibody cat# SP4558P

Staining of rat vas deferens using anti P2X1 antibody cat# RA10107

Staining of rat vas deferens using anti P2X1 antibody cat# RA10107

Staining of rat brainstem using anti P2X2 antibody cat# RA10108

Staining of rat brainstem using anti P2X2 antibody cat# RA10108

Staining of rat brainstem using anti P2Y2 antibody cat# RA14012

Staining of rat brainstem using anti P2Y2 antibody cat# RA14012

Table 1: Available Antibody Panel to Purinergic Receptors

Anti- P2Y1 (P2RY1), P2Y2 (P2RY2), P2Y4 (P2RY4), P2Y5 (P2RY5), P2Y6 (P2RY6), P2Y7 (P2RY7), P2Y8 (P2RY8), P2Y9 (P2RY9), P2Y10 (P2RY10), P2Y11 (P2RY11), P2Y12 (P2RY12), P2Y13 (P2RY13), P2Y14 (P2RY14), P2Y15 (P2RY15), P2X1 (P2RX1), P2X2 (P2RX2), P2X3 (P2RX3), P2X4 (P2RX4), P2X5 (P2RX5), P2X6 (P2RX6), P2X7 (P2RX7) antibody