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Titolo:
Activity of adenosine diphosphates and triphosphates on a P2Y(T)-type receptor in brain capillary endothelial cells
Autore:
Simon, J; Vigne, P; Eklund, KM; Michel, AD; Carruthers, AM; Humphrey, PPA; Frelin, C; Barnard, EA;
Indirizzi:
Univ Cambridge, Dept Pharmacol, Glaxo Inst Appl Pharmacol, Cambridge CB2 1QJ, England Univ Cambridge Cambridge England CB2 1QJ col, Cambridge CB2 1QJ, England CNRS UPR 411, Inst Pharmacol Mol & Cellulaire, F-06560 Valbonne, France CNRS UPR 411 Valbonne France F-06560 ellulaire, F-06560 Valbonne, France
Titolo Testata:
BRITISH JOURNAL OF PHARMACOLOGY
fascicolo: 1, volume: 132, anno: 2001,
pagine: 173 - 182
SICI:
0007-1188(200101)132:1<173:AOADAT>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
INDUCED PLATELET ACTIVATION; HUMAN BLOOD-PLATELETS; P2Y(1) RECEPTOR; ADP RECEPTORS; NUCLEOTIDE RECEPTORS; ADENYLATE-CYCLASE; MOLECULAR-BASIS; SHAPE CHANGE; ATP; IDENTIFICATION;
Keywords:
P2Y(T) receptor; P2Y(1) receptor; nucleotides; capillary endothelial cell; adenylyl cyclase inhibition;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
49
Recensione:
Indirizzi per estratti:
Indirizzo: Barnard, EA Univ Cambridge, Dept Pharmacol, Glaxo Inst Appl Pharmacol, Tennis Court Rd, Cambridge CB2 1QJ, England Univ Cambridge Tennis Court Rd Cambridge England CB2 1QJ land
Citazione:
J. Simon et al., "Activity of adenosine diphosphates and triphosphates on a P2Y(T)-type receptor in brain capillary endothelial cells", BR J PHARM, 132(1), 2001, pp. 173-182

Abstract

1 A. P2Y (nucleotide) receptor activity in a clonal population (B10) of rat brain capillary endothelial cells is coupled to inhibition of adenylyl cyclase and has functional similarities to the P2Y(T) (previously designated 'P2T') receptor for ADP of blood platelets. However, the only P2Y receptor which was detectable in a previous study of B10 cells by mRNA analysis was the P2Y(1) receptor, which elsewhere shows no transduction via cyclic nucleotides. We have sought here to clarify these issues.2 The inhibition of forskolin-stimulated adenylyl cyclase induced by purified nucleotides was measured on B10 cells. The EC50 value for 2-methylthioADP (2-MeSADP) was 2.2 nM and, surprisingly, 2-MeSATP was an almost equally strong agonist (EC50 = 3.5 nM). ATP and 2-ClATP were weak partial agonists (EC50 = 26 muM and 10 muM respectively) and under appropriate conditions could antagonise the activity on 2-MeSADP.3 A known selective antagonist of the platelet P2Y(T) receptor, 2-propylthioadenosine-5'-(beta,gamma)-difluoromethylene) triphosphonate (AR-C 66096),was a competitive antagonist of this B10 cell receptor, with pK(B) = 7.6. That ligand is inactive at the P2Y1 receptor in the same cells. Conversely,the competitive P2Y1 receptor antagonists, the 3', 5'- and 2', 5'-adenosine bis-monophosphates, are, instead, weak agonists at the adenylyl cyclase-inhibitory receptor.4 The inhibition of adenylyl cyclase by 2-MeSADP was completely abolished by pertussis toxin.5 In summary, these brain endothelial cells possess a P2Y(T)-type receptorin addition to the P2Y(1) receptor. The two have similarities in agonist profiles but are clearly distinguishable by antagonists and by their second messenger activations. The possible relationships between the B10 and platelet P2Y(T) receptors are discussed.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/01/20 alle ore 16:13:29