Pharmacological characterization of the human P2Y4 receptor.

Abstract

The P2Y4 receptor is a new member of the P2Y family which functionally behaves as a pyrimidinergic receptor. The pharmacological properties of the human P2Y4 receptor have been characterized following its stable expression in 1321N1 astrocytoma cells. UTP induced a biphasic accumulation of inositol trisphosphates, with an early peak at 30 s followed by a smaller but more sustained accumulation. ATP was a pure antagonist at early times and later behaved as a partial agonist. At 20 min, the rank order of potency of various nucleotides was the following: UTP > UDP = deoxy UTP > 5-bromo-UTP > ITP > ATP. Diadenosine polyphosphates also stimulated the production of inositol trisphosphates (after 20 min), more potently than ATP, but their maximal effect represented only 20-25% of that of UTP. Pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid inhibited strongly the UTP response, whereas suramin was inactive and reactive blue 2 had an intermediate effect. Pertussis toxin inhibited the response to UTP at early times (62 +/- 5% inhibition at 30 s), but its effect was no longer observed at 5 or 20 min. It is speculated that the P2Y4 receptor can exist in two distinct activation states differing in terms of time-course, specificity for uridine nucleotides and G-protein coupling.

• Authors: D Communi, S Motte, J M Boeynaems, S Pirotton
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 317 Issue 2-3 Pg. 383-9 (Dec 19 1996) ISSN: 0014-2999 [Print] Netherlands
• PMID: 8997625 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Nucleotides
• Purinergic P2 Receptor Agonists
• Purinergic P2 Receptor Antagonists
• Receptors, Purinergic P2
• Uracil Nucleotides
• Virulence Factors, Bordetella
• Adenosine Triphosphate
• Pertussis Toxin
• GTP-Binding Proteins
• Uridine Triphosphate

Topics

• Adenosine Triphosphate (metabolism)
• Astrocytoma (metabolism)
• Brain Neoplasms (metabolism)
• GTP-Binding Proteins (metabolism)
• Humans
• Nucleotides (metabolism)
• Pertussis Toxin
• Purinergic P2 Receptor Agonists
• Purinergic P2 Receptor Antagonists
• Radioligand Assay
• Receptors, Purinergic P2 (drug effects)
• Tumor Cells, Cultured
• Uracil Nucleotides (metabolism)
• Uridine Triphosphate (metabolism)
• Virulence Factors, Bordetella (pharmacology)