Pharmacological Characterization of the Human P2Y₁₃ Receptor

Abstract

The P2Y 13 receptor has recently been identified as a new P2Y receptor sharing a high sequence homology with the P2Y 12 receptor as well as similar functional properties: coupling to G i and responsiveness to ADP (Communi et al., 2001). In the present study, the pharmacology of the P2Y 13 receptor and its differences with that of the P2Y 12 Similarly, 2MeSADP was more potent than ADP in stimulating IP 3 accumulation after 10 min in AG32 cells and increasing cAMP in pertussis toxin-treated CHO-K1 cells stimulated by forskolin. On the other hand, ADP and 2MeSADP were equipotent at stimulating IP 3 formation in AG32 cells after 30 s and inhibiting forskolininduced cAMP accumulation in CHO-K1 cells. These differences in potency cannot be explained by differences in degradation rate, which in AG32 cells was similar for the two nucleotides. When contaminating diphosphates were enzymatically removed and assay of IP 3 was performed after 30 s, ATP and 2MeSATP seemed to be weak partial agonists of the P2Y 13 receptor expressed in AG32 cells. The stimulatory effect of ADP on the P2Y 13 receptor in AG32 cells was antagonized by reactive blue 2, suramin, pyridoxal-phosphate-6-azophenyl-2Ј,4Јdisulfonic acid, diadenosine tetraphosphate, and 2-(propylthio)-5Ј-adenylic acid, monoanhydride with dichloromethylenebis (phosphonic acid) (AR-C67085MX), but not by N 6

2,2′-Pyridylisatogen tosylate antagonizes P2Y1 receptor signaling without affecting nucleotide binding

“…However, the P2Y 1 receptor agonist radioligand has not been commercially available. Also, we did not measure the possible action (or lack of effect) of PIT on another ADP-preferring nucleotide receptor, the P2Y 13 subtype [17].…”

“…A functional assay of stimulation of adenylate cyclase via the hP2Y 12 receptor stably expressed in CHO cells was carried out in the presence of 10 μM forskolin by methods previously described [17].…”

Investigation of the functional expression of purine and pyrimidine receptors in porcine isolated pancreatic arteries

“…Molecular cloning has identified seven mammalian P2X receptor subunits: P2X1, P2X2, P2X3, P2X4, P2X5, P2X6 and P2X7 [3], while eight mammalian P2Y receptors have been identified: P2Y 1 , P2Y 2 , P2Y 4 , P2Y 6 , P2Y 11 , P2Y 12 , P2Y 13 and P2Y 14 [4]. P2X receptors are activated by adenosine-5′-triphosphate (ATP) and its stable, and consequently more potent, analogue αβ-methylene-ATP (αβ-meATP) [5,6].…”

“…Among the adenine nucleotide group, the human P2Y 11 receptor is selectively activated by ATP and fails to respond to adenosine-5′-diphosphate (ADP) [8], although the dog orthologue responds to both ADP and ATP [9]. P2Y 1 , P2Y 12 and P2Y 13 receptors are activated by ADP and, with lower potency, by ATP [10][11][12][13]. Among the uracil nucleotide or UDP-sugar receptors, the P2Y 2 receptor is equally activated by ATP and uridine-5′-triphosphate (UTP), while the P2Y 4 receptor is highly selective for UTP over ATP [14].…”

Ligand-gated Ion Channels

“…Rank order of potency ATP > UTP ADP >> ATP ADP >> ATP UDP-glucose Selective agonists ARC67085 (Communi et al, 1999), NAD + (Moreschi et al, 2006), NAADP + (Moreschi et al, 2008), NF546 (Meis et al, 2010) ADP, 2-MeSADP -MRS2690 (Ko et al, 2007) Selective antagonists NF157 (Ullmann et al, 2005) ATP, ARL66096 (Humphries et al, 1995) MRS2211 -ARC69931MX shows selectivity for P2Y12 and P2Y13 receptors compared to other P2Y receptors (Marteau et al 2003;Takasaki et al, 2001). NF157 also has antagonist activity at P2X1 receptors (Ullmann et al, 2005).…”