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Regulation of cyclic AMP by extracellular ATP in cultured brain capillary endothelial cells
Author(s) -
Anwar Zubeya,
Albert Jennifer L,
Gubby Sharon E,
Boyle John P,
Roberts Jonathon A,
Webb Tania E,
Boarder Michael R
Publication year - 1999
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 - 10.1038/sj.bjp.0702792
Subject(s) - adenosine , adenosine deaminase , forskolin , p2y receptor , adenosine a2b receptor , medicine , nucleotide , endocrinology , receptor , adenosine a1 receptor , purinergic signalling , biology , extracellular , cgs 21680 , adenine nucleotide , adenylate kinase , p2 receptor , amp deaminase , adenylyl cyclase , adenosine receptor , biochemistry , purinergic receptor , agonist , gene
In primary unpassaged rat brain capillary endothelial cell cultures (RBECs), using reverse‐transcriptase PCR with primers specific for P2Y receptor subtypes, we detected mRNA for P2Y 2 , P2Y 4 and P2Y 6 , but not P2Y 1 receptors. None of the various nucleotides tested reduced forskolin elevated cyclic AMP levels in RBECs. ATP and ATPγS, as well as adenosine, enhanced cyclic AMP accumulation in the presence of forskolin. Comparison of the concentration response curves to ATPγS with those for ATP and adenosine, at different incubation times, indicated that the response to purine nucleotides was not wholly dependent on conversion to adenosine. Adenosine deaminase abolished the response to adenosine but only reduced the response to ATP by about 50%. These results suggest the participation of a receptor responsive to nucleotides. Isobutylmethylxanthine and 8‐sulphophenyltheophylline prevented the cyclic AMP response, while neither 8‐cyclopentyl‐1,3‐dipropylxanthine nor SCH58261 were effective antagonists. 2‐chloradenosine gave a robust response, but neither 2‐chloro‐N 6 ‐cyclopentyladenosine nor CGS 21680 were agonists. These results show that adenosine and ATP can elevate the cyclic AMP levels of brain endothelial cells by acting on receptors which have a pharmacology apparently distinct from known P2Y and adenosine receptors.British Journal of Pharmacology (1999) 128 , 465–471; doi: 10.1038/sj.bjp.0702792