Platelets in Nonresponders to Epinephrine Stimulation Showed Reduced Response to ADP

It has been reported that platelets from some healthy donors did not respond to epinephrine (Epi). To identify the cause for the lack of response, we examined the α 2 adrenoceptor in the platelets and their signal transduction pathways. No differences in the genomic (−2076 to 1526 bp) and coding reg...

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Bibliographic Details
Published in:Thrombosis research 2001-10, Vol.104 (2), p.127-135
Main Authors: Nakahashi, Takeshi K., Kambayashi, Jun-ichi, Nakamura, Takashi, Le, Sang N., Yoshitake, Masuhiro, Tandon, Narendra N., Sun, Bing
Format: Article
Language:English
Subjects:
Adenosine Diphosphate - pharmacology
Adrenergic alpha-Agonists - pharmacology
Adrenoceptor
Aggregation
Base Sequence
Binding Sites
Biological and medical sciences
Blood Platelets - drug effects
Cyclic AMP - metabolism
Dose-Response Relationship, Drug
Drug Resistance
Epinephrine - pharmacology
Fundamental and applied biological sciences. Psychology
G i protein
Humans
Membrane Proteins
Platelet Aggregation - drug effects
Purinergic P2 Receptor Antagonists
Receptors, Adrenergic, alpha-2 - genetics
Receptors, Adrenergic, alpha-2 - metabolism
Receptors, Adrenergic, alpha-2 - physiology
Receptors, Purinergic P2 - metabolism
Receptors, Purinergic P2Y12
Signal Transduction
Vertebrates: blood, hematopoietic organs, reticuloendothelial system
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Summary:It has been reported that platelets from some healthy donors did not respond to epinephrine (Epi). To identify the cause for the lack of response, we examined the α 2 adrenoceptor in the platelets and their signal transduction pathways. No differences in the genomic (−2076 to 1526 bp) and coding region of α 2A adrenoceptor complementary DNA (cDNA) were found between the responders (R) and nonresponders (NR). No expression of α 2B or α 2C adrenoceptor was detected in platelets. When UK14,304 was used to induce platelet aggregation, similar effect to Epi was observed between R and NR, and any involvement of the α 1 and β adrenoceptor was ruled out. Radioligand binding assay showed similar number of α 2 binding sites between the two groups (139±25/platelet vs. 145±37/platelets). However, platelets from NR showed a weaker response to adenosine diphosphate (ADP, 52.3±17.8% vs. 80.5±8.7% from R, P
ISSN:0049-3848
1879-2472
DOI:10.1016/S0049-3848(01)00354-1