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Purinergic Receptor P2y, G Protein-coupled, 2 OKDB#: 919
 Symbols: P2RY2 Species: human
 Synonyms: PURINOCEPTOR P2Y2, P2Y2, P2Y2R| P2U NUCLEOTIDE RECEPTOR, P2UR|  Locus: 11q13.5 in Homo sapiens
HPMR


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General Comment ATP is known to depolarize sensory neurons and may play a role in nociceptor activation when released from damaged tissue. Cell surface ATP receptors can be divided into 2 classes. The ionotropic (P2X) class are ligand-gated channels. The metabotropic (P2Y/P2U) class are members of the 7-transmembrane superfamily of G protein-coupled receptors The G-protein-coupled P2Y purinoceptors mediate a variety of physiological effects in response to extracellular nucleotides. With the recent discovery of several new members from a variety of species, the P2Y purinoceptor family now encompasses types P2Y1 to P2Y6.

NCBI Summary: The product of this gene belongs to the family of G-protein coupled receptors. This family has several receptor subtypes with different pharmacological selectivity, which overlaps in some cases, for various adenosine and uridine nucleotides. This receptor is responsive to both adenosine and uridine nucleotides. It may participate in control of the cell cycle of endometrial carcinoma cells. Three transcript variants encoding the same protein have been identified for this gene.
General function Receptor
Comment
Cellular localization Plasma membrane
Comment
Ovarian function Follicle development, Antral follicle growth
Comment Janssens R, et al 2000 reported cloning and tissue distribution of the human P2Y1 receptor. Northern blot analysis detected a 6.7 kilobase messenger RNA in most human tissues, the strongest signals being observed in prostate and ovary.
Expression regulated by LH
Comment
Ovarian localization Granulosa, Theca, Luteal cells
Comment Functional expression and intracellular signaling of UTP-sensitive P2Y receptors in theca-interstitial cells. Vazquez-Cuevas FG et al. ABSTRACT: BACKGROUND: Purinergic receptors are expressed in the ovary of different species; their physiological roles remain to be elucidated. UTP-sensitive P2Y receptor activity may regulate cell proliferation. The aim of the present work was to study the functional expression of these receptors in theca/interstitial cells (TIC). METHODS: TIC were isolated by centrifugation in a Percoll gradient. P2Y receptors and cellular markers in TIC were detected by RT-PCR and Western blot. Intracellular calcium mobilization induced by purinergic drugs was evaluated by fluorescence microscopy, phosphorylation of MAPK p44/p42 and of cAMP response element binding protein (CREB) was determined by Western blot and proliferation was quantified by 3H]-thymidine incorporation into DNA. RESULTS: RT-PCR showed expression of p2y2r and p2y6r transcripts, expression of the corresponding proteins was confirmed. UTP and UDP, agonists for P2Y2 and P2Y6 receptors, induced an intracellular calcium increase with a maximum of more than 400% and 200% of basal level, respectively. The response elicited by UTP had an EC50 of 3.5 +/- 1.01 uM, while that for UDP was 3.24 +/- 0.82 uM. To explore components of the pathway activated by these receptors, we evaluated the phosphorylation induced by UTP or UDP of MAPK p44 and p42. It was found that UTP increased MAPK phosphorylation by up to 550% with an EC50 of 3.34 +/- 0.92 and 1.41 +/- 0.67 uM, for p44 and p42, respectively; these increases were blocked by suramin. UDP also induced p44/p42 phosphorylation, but at high concentrations. Phosphorylation of p44/p42 was dependent on PKC and intracellular calcium. To explore possible roles of this pathway in cell physiology, cell proliferation and hCG-induced CREB-phosphorylation assays were performed; results showed that agonists increased cell proliferation and prevented CREB-phosphorylation. CONCLUSION: Here, it is shown that UTP-sensitive P2Y receptors are expressed in cultured TIC and that these receptors had the ability to activate mitogenic signaling pathways and to promote cell proliferation, as well as to prevent CREB-phosphorylation by hCG. Regulation of TIC proliferation and steroidogenesis is relevant in ovarian pathophysiology since theca hyperplasia is involved in polycystic ovarian syndrome. Purinergic receptors described might represent an important new set of molecular therapeutic targets. [Tai CJ, et al 2000 examined the expression and regulation of the P2U purinergic receptor (P2UR) in human granulosa-luteal cells (hGLCs) by RT-PCR and Northern blot analysis. Two mRNA transcripts of 2.0 kb and 4.6 kb were identified in hGLCs using Northern blot analysis. The expression of the P2UR mRNA was down-regulated by human CG in a dose- and time-dependent manner. Treatment with 8-bromo-cAMP and forskolin also attenuated P2UR mRNA levels. Calcium signaling following the activation of the P2UR in single hGLCs was studied using microspectrofluorimetry. It revealed that, like ATP, uridine triphosphate (UTP) also induced cytosolic calcium mobilization in a dose-dependent manner. The P2UR expressed in hGLCs is functional because activation of the P2UR by ATP or UTP resulted in rapid and transient mobilization of cytosolic calcium at the single cell level.
Follicle stages Antral, Preovulatory, Corpus luteum
Comment
Phenotypes
Mutations 0 mutations
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created: April 22, 2000, midnight by: hsueh   email:
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last update: July 21, 2010, 3:36 p.m. by: hsueh    email:



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