ADP Acting on P2Y13 Receptors Is a Negative Feedback Pathway for ATP Release From Human Red Blood Cells.
Författare
Summary, in English
Red blood cells may regulate tissue circulation and O-2 delivery by releasing the vasodilator ATP in response to hypoxia. When released extracellularly, ATP is rapidly degraded to ADP in the circulation by ectonucleotidases. In this study, we show that ADP acting on P2Y(13) receptors on red blood cells serves as a negative feedback pathway for the inhibition of ATP release. mRNA of the ADP receptor P2Y(13) was highly expressed in human red blood cells and reticulocytes. The stable ADP analogue 2-MeSADP decreased ATP release from red blood cells by inhibition of cAMP. The P2Y(12) and P2Y(13) receptor antagonist AR-C67085 (30 mumol/L), but not the P2Y(1) blocker MRS2179, inhibited the effects of 2-MeSADP. At doses where AR-C67085 only blocks P2Y(12) (100 nmol/L), it had no effect. AR-C67085 and the nucleotidase apyrase increased cAMP per se, indicating a constant cAMP inhibitory effect of endogenous extracellular ADP. 2-MeSADP reduced plasma ATP concentrations in an in vivo pig model. Our results indicate that the ATP degradation product ADP inhibits ATP release by acting on the red blood cell P2Y(13) receptor. This negative feedback system could be important in the control of plasma ATP levels and tissue circulation.
Avdelning/ar
Publiceringsår
2005
Språk
Engelska
Sidor
189-196
Publikation/Tidskrift/Serie
Circulation Research
Volym
96
Issue
Dec 16
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
American Heart Association
Ämne
- Cardiac and Cardiovascular Systems
Nyckelord
- microdialysis
- ATP release
- cAMP
- red blood cells
- P2 receptors
Status
Published
Forskningsgrupp
- Transfusion Medicine
ISBN/ISSN/Övrigt
- ISSN: 0009-7330