ATP, a partial agonist of atypical P2Y purinoceptors in rat brain microvascular endothelial cells.
1. Purinoceptor responses were analyzed in B10 cells, a clonal population of rat brain capillary endothelial cells. 2. B10 cells lack P2U receptors as evidenced by the lack of UTP responses and the failure to amplify P2U-related sequences by polymerase chain reaction. 3. B10 cells responded to adenine nucleotides by large increases in [Ca2+]i. Half maximum effective concentrations were 2-methylthio-ATP: 180 nM > 2-chloro-ATP: 310 nM = ADP: 330 nM > adenosine 5'-O-(3-thiotrisphosphate): 2.3 microM = ATP: 2.7 microM. The maximum response to ATP was only 55% of that to ADP while that to ATP derivatives was 75%. 4. The actions of adenine nucleotides were not associated with a measurable activation of phospholipase C. 5. Cross desensitizations of the actions of ADP and ATP were observed. 6. In additivity experiments, ADP superposed its action on top of that of ATP and ATP partially inhibited the action of ADP. 7. It is concluded that ATP acts as a partial agonist of the P2Y-like receptor of brain capillary endothelial cells.
Feolde
E
E
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS, Université de Nice-Sophia Antipolis, Valbonne, France.
Vigne
P
P
Breittmayer
J P
JP
Frelin
C
C
D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000098:blood supply / Q000187:drug effects*; D002196:Capillaries / Q000166:cytology / Q000187:drug effects; D002478:Cells, Cultured; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D008969:Molecular Sequence Data; D058910:Purinergic P2 Receptor Agonists; D051381:Rats
D017931:DNA Primers; D058910:Purinergic P2 Receptor Agonists; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate