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ADP Acting on P2Y13 Receptors Is a Negative Feedback Pathway for ATP Release From Human Red Blood Cells.

Wang, Lingwei LU ; Olivecrona, Göran LU ; Götberg, Matthias LU ; Olsson, Martin L LU ; Sörhede Winzell, Maria LU and Erlinge, David LU (2005) In Circulation Research 96(Dec 16). p.189-196
Abstract
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
microdialysis, ATP release, cAMP, red blood cells, P2 receptors
in
Circulation Research
volume
96
issue
Dec 16
pages
189 - 196
publisher
American Heart Association
external identifiers
  • pmid:15604418
  • wos:000226794300009
  • scopus:13444249474
ISSN
0009-7330
DOI
10.1161/01.RES.0000153670.07559.E4
language
English
LU publication?
yes
id
a03b4f0d-2dea-4ff0-8347-268b96a7bfad (old id 131987)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15604418&dopt=Abstract
date added to LUP
2007-07-02 13:25:40
date last changed
2017-09-03 04:37:47
@article{a03b4f0d-2dea-4ff0-8347-268b96a7bfad,
  abstract     = {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.},
  author       = {Wang, Lingwei and Olivecrona, Göran and Götberg, Matthias and Olsson, Martin L and Sörhede Winzell, Maria and Erlinge, David},
  issn         = {0009-7330},
  keyword      = {microdialysis,ATP release,cAMP,red blood cells,P2 receptors},
  language     = {eng},
  number       = {Dec 16},
  pages        = {189--196},
  publisher    = {American Heart Association},
  series       = {Circulation Research},
  title        = {ADP Acting on P2Y13 Receptors Is a Negative Feedback Pathway for ATP Release From Human Red Blood Cells.},
  url          = {http://dx.doi.org/10.1161/01.RES.0000153670.07559.E4},
  volume       = {96},
  year         = {2005},
}