Platelets in nonresponders to epinephrine stimulation showed reduced response to ADP

It has been reported that platelets from some healthy donors did not respon d to epinephrine (Epi). To identify the cause for the lack of response, we examined the alpha (2) adrenoceptor in the platelets and their signal trans duction pathways. No differences in the genomic (-2076 to 1526 bp) and codi ng region of alpha (2A) adrenoceptor complementary DNA (cDNA) were found be tween the responders (R) and nonresponders (NR). No expression of alpha (2B ) or alpha (2C) adrenoceptor was detected in platelets. When UK14,304 was u sed to induce platelet aggregation, similar effect to Epi was observed betw een R and NR, and any involvement of the alpha (1) and beta adrenoceptor wa s ruled out. Radioligand binding assay showed similar number of alpha (2) b inding sites between the two groups (139 +/- 25/platelet vs. 145 +/- 37/pla telets). However, platelets from NR showed a weaker response to adenosine d iphosphate (ADP, 52.3 +/- 17.8% vs. 80.5 +/- 8.7% from R, P < .01). In the presence of P2Y(1) antagonist adenosine 3',5'-diphosphosulfate (A3P5PS), AD P failed to induce platelet aggregation in NR (7.8 +/- 4.7% vs. 64.7 +/- 11 .2% in R, P < .01). Addition of SQ22,536 to inhibit adenylyl cyclase did no t convert NR to R. These observations demonstrate that there is an impaired platelet responsiveness to ADP as well as to Epi in NR, due to a differenc e in downstream of the signal transduction pathway but independent of adeny lyl cyclase inhibition. (C) 2001 Elsevier Science Ltd. All rights reserved.