A Molecularly Identified P2Y Receptor Simultaneously Activates Phospholipase C and Inhibits Adenylyl Cyclase and Is Nonselectively Activated by All Nucleoside Triphosphates
We recently cloned and expressed a novel P2Y receptor (tp2y receptor) from a turkey cDNA library. Expression of this receptor in 1321N1 human astrocytoma cells confers nucleotide-dependent stimulation of phospholipase C activity; however, as we demonstrate here, it also confers nucleotide-dependent...
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Published in | Molecular pharmacology Vol. 57; no. 4; pp. 805 - 810 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Pharmacology and Experimental Therapeutics
01.04.2000
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Subjects | |
Online Access | Get full text |
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Summary: | We recently cloned and expressed a novel P2Y receptor (tp2y receptor) from a turkey cDNA library. Expression of this receptor
in 1321N1 human astrocytoma cells confers nucleotide-dependent stimulation of phospholipase C activity; however, as we demonstrate
here, it also confers nucleotide-dependent inhibition of adenylyl cyclase. Both the phospholipase C and adenylyl cyclase responses
were promoted by receptor agonists over a similar range of concentrations. Moreover, not only did UTP and ATP activate the
avian receptor but ITP, GTP, xanthosine 5â²-triphosphate, and CTP were also agonists, with EC 50 values ranging between 0.1 and 1 μM. Similar potencies, rank-order, and selectivity of nucleotide agonists were also demonstrated
for intracellular Ca 2+ mobilization measured during a 30-s stimulation under constant superfusion conditions. This observation indicates that receptor
activation by nucleoside 5â²-triphosphates is not produced by interconversion of these nucleotides into ATP or UTP. Pretreatment
of cells with pertussis toxin completely abolished the inhibitory effect of nucleotide agonists on adenylyl cyclase, whereas
the activation of phospholipase C was only partially inhibited. These results demonstrate that the avian P2Y receptor is a
nucleoside triphosphate receptor of broad agonist selectivity that interacts with both pertussis toxin-insensitive and -sensitive
G proteins to activate phospholipase C and to inhibit adenylyl cyclase. This is the first cloned P2Y receptor that is clearly
Gi/adenylyl cyclase-linked. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0026-895X 1521-0111 |
DOI: | 10.1124/mol.57.4.805 |