Premium
Pharmacological selectivity of the cloned human P 2U ‐purinoceptor: potent activation by diadenosine tetraphosphate
Author(s) -
Lazarowski Eduardo R.,
Watt William C.,
Stutts M. Jackson,
Boucher Richard C.,
Harden T. Kendall
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb16382.x
Subject(s) - purinergic receptor , agonist , phospholipase c , inositol , ppads , pharmacology , chemistry , inositol phosphate , p2y receptor , biochemistry , adenosine , receptor , biology
1 The human P 2U ‐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 P 2U ‐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 ATPγS were full and potent agonists for activation of phospholipase C with EC 50 values of 140 nM, 230 nM, and 1.72 μ M , 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 P 2Y ‐, P 2X ‐, and P 2T ‐purinoceptor agonists, 2MeSATP, α,β‐MeATP, and 2MeSADP, respectively. 4 Diadenosine tetraphosphate, Ap 4 A, was a surprisingly potent agonist at the expressed P 2U ‐purinoceptor with an EC 50 (720 nM) in the range of the most potent P 2U ‐purinoceptor agonists. AP4A may be a physiologically important activator of P 2U ‐purinoceptors.