ADP-induced platelet shape change and mobilization of cytoplasmic ionized
calcium are mediated by distinct binding sites on platelets: 5'-
p-fluorosulfonylbenzoyladenosine is a weak platelet agonist
AK Rao and MA Kowalska
Platelet stimulation with ADP results in several responses, including shape
change, increase in cytoplasmic ionized calcium concentration [Ca2+]i, an
inhibition of adenylate cyclase. 5'-p-Fluorosulphonyl benzoyladenosine
(FSBA), which covalently labels an ADP binding site on platelets, blocks
platelet shape change but not the inhibition of cyclic AMP levels by ADP,
whereas p-chloromercuribenzenesulfonate (pCMBS), a nonpenetrating thiol
reagent, has the opposite effects. We examined the effect of FSBA and pCMBS
on ADP-induced increase in [Ca2+]i using platelets loaded with fluorescent
Ca2+ indicators quin2 and fura-2. FSBA (50 to 200 mumol/L) induced a
dose-dependent rise in [Ca2+]i, indicating that it is a weak platelet
agonist. Under conditions of covalent labeling of the ADP binding sites,
FSBA (50 to 100 mumol/L) did not inhibit the ADP-induced increase in
[Ca2+]i or its inhibition of adenylate cyclase, whereas pCMBS (up to 1
mmol/L) abolished both these responses but not shape change. These findings
suggest that ADP-induced Ca2+ mobilization and inhibition of adenylate
cyclase are mediated by platelet binding sites distinct from those
mediating shape change.
Volume 70,
Issue 3,
pp. 751-756,
09/01/1987
Copyright © 1987 by The American Society of Hematology
