Synergistic effects of butyrate on platelet responses to arachidonate,
A23187, PGE1, and forskolin
NN Tandon, TS Tralka and GA Jamieson
With eukaryotic cells, butyrate is known to induce a series of
morphological and biochemical changes that mimic cellular differentiation.
With platelets, we have found that butyrate (10 mmol/L) caused an
approximately threefold increase in sensitivity to calcium ionophore A23187
and arachidonate. Maximum aggregation was observed at agonist
concentrations of 3 mumol/L and 170 mumol/L, respectively, as compared with
required concentrations of 10 mumol/L and 400 mumol/L in the absence of
butyrate. Similar effects were seen with isobutyric acid, and about
one-half the effect was shown with valerate and caproate, but lower
homologues showed no synergistic effect. No ultrastructural changes were
observed in platelets incubated with butyrate, and the aggregation effects
were reversible and returned to normal on removal of butyrate. Membrane
fluidity was unchanged by butyrate as measured by changes in the
fluorescence depolarization of diphenylhexatriene. Butyrate caused a 60% to
70% increase in the uptake of 3H-arachidonate. Butyrate also potentiated
the inhibition of platelet function by prostaglandin E1 and forskolin and
uptake of 3H- forskolin was increased approximately 20%. In contrast,
platelet response to other agonists (ADP, epinephrine, collagen, thrombin,
and platelet-activating factor) was essentially unaffected by butyrate.
These results suggest that butyrate may increase the uptake of certain
hydophobic agonists and antagonists by platelets. Similar mechanisms for
uptake of endogenous effectors may explain the response of eukaryotic cells
to butyrate in culture.
Volume 67,
Issue 2,
pp. 366-372,
02/01/1986
Copyright © 1986 by The American Society of Hematology
