The platelet strip. II. Pharmacomechanical coupling in thrombin-activated human platelets.

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.