HETEROGENEITY OF THE AGGREGATION RESPONSE OF HUMAN PLATELETS TO ARGININE-VASOPRESSIN

Previous reports have alluded to variability in the aggregation respon se of normal human platelets to the neuropeptide arginine vasopressin (AVP), Since it has not been well documented, the current studies were undertaken to characterize this response, AVP (1-100 nM) produced a c oncentration-dependent aggregation response. Although the aggregation response to 100 nM AVP did not correlate with age or sex, there was a bimodal response distribution based on the presence or absence of a se cond wave of aggregation, In kinetic studies, the apparent km of AVP w as 18.3 +/- 5.4 nM, There was a significant inverse relationship betwe en the maximal aggregation response to 100 nM AVP and the km (r = -0.8 2), One hundred nanomolar AVP increased the intracellular calcium conc entration of platelets by 406 +/- 120 nM in calcium free buffer and by 658 +/- 233 nM in the presence of 1.0 mM CaCl2. The aggregation respo nse to 100 nM AVP correlated most strongly with the transmembrane infl ux of calcium (r = 0.84), In individuals whom 100 nM AVP was able to g enerate a second wave of aggregation, the selective protein kinase C i nhibitor bis-indolylmaleimide significantly decreased the platelet agg regation response. Thus, there is significant heterogeneity in the agg regation response of normal human platelets to AVP. Based on our kinet ic studies and the effects of PKC inhibition on the aggregation respon se to AVP, we would hypothesize that the variability of the aggregatio n response of normal human platelets to AVP is related to a polymerphi sm of the platelet AVP V-1 receptor. (C) 1995 Wiley-Liss, Inc.