AJP - Cell Physiology, Vol 249, Issue 3 288-C296, Copyright © 1985 by American Physiological Society
The platelet strip. II. Pharmacomechanical coupling in thrombin-activated human platelets
L. Salganicoff and R. W. Sevy
A model of contracted, irreversibly aggregated thrombin-activated human
platelets relaxes when treated with
ethyleneglycol-bis(beta-aminoethylether-N,N'-tetraacetic acid (EGTA) in the
presence of Mg2+. Inhibition of the cyclooxygenase or blockade of the
thromboxane A2 receptor decreases the tension partially, but EGTA treatment
is needed for full relaxation. After a stable relaxation has been achieved
(3-4 h), Ca2+ addition in a cumulative manner does not reinduce
contraction. Whether in the absence or presence of external Ca2+, the
relaxed preparation contracts when stimulated with ADP, epinephrine,
thromboxane A2 or its analogues, or thrombin. At supramaximal doses, each
of the agonists activates only a partial amount of the total tension
capable of being generated. Addition of an agonist of a different class to
the partially contracted preparation further increases its force. The
contractile responses are reversible on washout, with kinetics dependent on
the class of agonist and time of contact with the preparation. The
contraction induced by the prolonged simultaneous stimulation with ADP,
arachidonate, and thrombin reverts very slowly on washout of the agonists
and for all practical purposes reproduces the initial state of irreversible
platelet contraction.
