Intercalation of amphipaths into the plasma membrane of platelets has
a marked effect on their morphology. Incubation of platelets with phos
phatidylcholines (PC) results in rounding of the platelet body and spi
culation, while incubation with aminophospholipids such as dilauroylph
osphatidylserine (DLPS) results in a biphasic shape change consistent
with the bilayer couple model (Sheetz, M.P. and Singer, S.J. (1982) Pr
oc. Natl. Acad. Sci. USA 71, 4457-4461) and with the activity of an am
inophospholipid translocator facilitating transverse bilayer diffusion
(Daleke, D.L. and Huestis, W.H. (1985) Biochemistry 24, 5406-5416). T
he present study extends this work to investigate the effects of PC an
d PS on platelet responses to a natural agonist, thrombin. PC incorpor
ation produces a concentration-dependent progression of shape changes,
beginning with surface ruffling and development of fine spicules, fol
lowed by sphering of the cell body, and ending with the apparent loss
of spicules. PC reduces platelet responses to thrombin only under cond
itions that promote membrane vesiculation, seen morphologically as a l
oss of spicules and biochemically as a loss of C-14-PC labeled membran
e. PS homologues of varying acyl chain composition induce concentratio
n- and time-dependent platelet sphering. Incorporation of PS inhibits
thrombin-induced platelet shape change, granule secretion, and protein
phosphorylation. Inhibition of these responses requires transit of th
e exogenous PS to the cytofacial leaflet of the membrane bilayer.