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PMID: 8564228 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Pharmacological selectivity of the cloned human P2U-purinoceptor: potent activation by diadenosine tetraphosphate.

British journal of pharmacology ·Vol. 116 ·No. 1 ·1995-09-00 ·Pages 1619-27

Lazarowski ER, Watt WC, Stutts MJ, Boucher RC, Harden TK

Abstract

1. The human P2U-purinoceptor was stably expressed in 1321N1 human astrocytoma cells and the pharmacological selectivity of the expressed receptor was studied by measurement of inositol lipid hydrolysis. 2. High basal levels of inositol phosphates occurred in P2U-purinoceptor-expressing cells. This phenomenon was shown to be due to release of large amounts of ATP from 1321N1 cells, and could be circumvented by adoption of an assay protocol that did not involve medium changes. 3. UTP, ATP and ATP gamma S were full and potent agonists for activation of phospholipase C with EC50 values of 140 nM, 230 nM, and 1.72 microM, respectively. 5BrUTP, 2C1ATP and 8BrATP were also full agonists although less potent than their natural congeners. Little or no effect was observed with the selective P2Y-, P2X-, and P2T-purinoceptor agonists, 2MeSATP, alpha,beta-MeATP, and 2MeSADP, respectively. 4. Diadenosine tetraphosphate, Ap4A, was a surprisingly potent agonist at the expressed P2U-purinoceptor with an EC50 (720 nM) in the range of the most potent P2U-purinoceptor agonists. Ap4A may be a physiologically important activator of P2U-purinoceptors.

MeSH Terms
Adenine/metabolism Adenine Nucleotides/metabolism Astrocytoma/genetics,metabolism Cloning, Molecular Dinucleoside Phosphates/pharmacology Humans Inositol Phosphates/metabolism Purinergic P2 Receptor Agonists Receptors, Purinergic P2/genetics,physiology Second Messenger Systems Sensitivity and Specificity Transfection Tritium Tumor Cells, Cultured Uridine Triphosphate/pharmacology
Chemicals
Adenine Nucleotides Dinucleoside Phosphates Inositol Phosphates Purinergic P2 Receptor Agonists Receptors, Purinergic P2 Tritium diadenosine tetraphosphate Adenine Uridine Triphosphate
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Lazarowski E R
Department of Pharmacology, University of North Carolina, School of Medicine, Chapel Hill 27599, USA.
Watt W C
Stutts M J
Boucher R C
Harden T K
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Article Info
Journal
British journal of pharmacology
Abbr.
Br J Pharmacol
ISSN
0007-1188
DOI
10.1111/j.1476-5381.1995.tb16382.x
Published
1995-09-00
Pages
1619-27
Language
English
Region
England
NLM ID
7502536
PMCID
PMC1908898
Subset
IM
Grants
NIGMS NIH HHS · GM29536 · United States
NIGMS NIH HHS · GM38213 · United States
NHLBI NIH HHS · HL34322 · United States
External Links
PubMed source DOI: 10.1111/j.1476-5381.1995.tb16382.x PMC Full Text View journal details
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