In:
British Journal of Pharmacology, Wiley, Vol. 135, No. 2 ( 2002-01), p. 363-372
Abstract:
We have examined the role of ATP‐dependent P2X 1 receptors in megakaryocytes (MKs) and platelets using receptor‐deficient mice and selective agonists. α,β‐meATP‐ and ATP‐ evoked ionotropic inward currents were absent in whole‐cell recordings from MKs of P2X 1 −/− mice, demonstrating that the P2X receptor phenotype in MKs, and by inference, platelets, is due to expression of homomeric P2X 1 receptors. P2X 1 receptor deficiency had no effect on MK (CD 41) numbers or size distribution, showing that it is not essential for normal MK development. P2Y receptor‐stimulated [Ca 2+ ] i responses were unaffected in MKs from P2X 1 −/− mice, however the inward cation current associated with Ca 2+ release was reduced by ∼50%, suggesting an interaction between the membrane conductances activated by P2X 1 and P2Y receptors. Interaction between P2X 1 and P2Y receptors in human platelets was also examined using [Ca 2+ ] i recordings from cell suspensions. α,β‐meATP (10 μ M ) evoked a rapid transient P2X 1 receptor‐mediated increase in [Ca 2+ ] i , whereas ADP‐(10 μ M ) evoked P2Y receptor responses were slower, peaked at a higher level and remained elevated for longer periods. Co‐application of α,β‐meATP and ADP resulted in marked acceleration and amplification of the peak [Ca 2+ ] i response. We conclude that ionotropic P2X 1 receptors may play a priming role in the subsequent activation of metabotropic P2Y receptors during platelet stimulation. British Journal of Pharmacology (2002) 135 , 363–372; doi: 10.1038/sj.bjp.0704486
Type of Medium:
Online Resource
ISSN:
0007-1188
,
1476-5381
DOI:
10.1038/sj.bjp.0704486
Language:
English
Publisher:
Wiley
Publication Date:
2002
detail.hit.zdb_id:
2029728-2
SSG:
15,3
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