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Differential requirements for platelet aggregation and inhibition of
adenylate cyclase by epinephrine. Studies of a familial platelet alpha
2-adrenergic receptor defect
AK Rao, J Willis, MA Kowalska, YT Wachtfogel and RW Colman
Thrombosis Research Center, Temple University School of Medicine,
Philadelphia, PA.
We describe a family whose members have impaired platelet aggregation and
secretion responses to epinephrine with normal responses to adenosine
diphosphate and collagen. Platelet alpha 2-adrenergic receptors (measured
using 3H methyl-yohimbine) were diminished in the propositus (78 sites per
platelet), his two sisters (70 and 27 sites per platelet), and parents (37
and 63 sites per platelet), but not in two maternal aunts (12 normal
subjects, 214 +/- 18 sites per platelet; mean +/- SE). However, the
inhibition of cyclic adenosine monophosphate (cAMP) levels by epinephrine
in platelets exposed to 400 nmol/L PGI2 was similar in the patients and
five normal subjects (epinephrine concentration for 50% inhibition, 0.04
+/- 0.01 mumol/L v 0.03 +/- 0.01 mumol/L; P greater than .05). In normal
platelets, the concentration of yohimbine (0.18 mumol/L) required for half
maximal inhibition of aggregation induced by 2 mumol/L epinephrine was
lower than that for inhibition of its effect on adenylate cyclase (1.6
mumol/L). In quin2 loaded platelets, thrombin (0.1 U/mL) stimulated rise in
cytoplasmic Ca2+ concentration, [Ca2+]i, was normal in the two patients
studied. The PGI2 analog ZK 36,374 completely inhibited thrombin-induced
rise in [Ca2+]i; the reversal of this inhibition by epinephrine was normal
in the two patients. Thus, despite the impaired aggregation response to
epinephrine, platelets from these patients have normal ability to inhibit
PGI2-stimulated cAMP levels. These patients with an inherited receptor
defect provide evidence that fewer platelet alpha 2-adrenergic receptors
are required for epinephrine-induced inhibition of adenylate cyclase than
for aggregation.
Volume 71,
Issue 2,
pp. 494-501,
02/01/1988
Copyright © 1988 by The American Society of Hematology
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