Platelet-Platelet Contact is Required to Observe Guanylate Cyclase Activation in Stimulated Platelets

Abstract

Increases in [cyclic-3',5'-GMP] in aspirin-treated platelet-rich plasma and washed platelet preparations resulted from stimulation by all excitatory agonists tested, and by other agents which induced aggregate formation. The maximal increase observed was approximately 4-fold above the resting level. The increase in [cyclic-3',5'-GMP] correlated closely in both time-, and agonist dose-dependence with aggregation as measured by an increase in light transmittance. It was delayed in time, and occurred at a higher agonist concentration, than the initial phase of aggregation as measured by loss of single platelets. The extent of increase in [cyclic-3',5'-GMP] was independent of the signal transduction pathway used by the agonist/agent. Inhibition of aggregation by removal of Ca(2+), failure to induce contact, addition of antibodies or antagonists to the glycoprotein IIb/IIIa complex or the presence of an inhibitory agonist such as PGI(2) prevented the increase in [cyclic-3',5'-GMP]. Contact with collagen fibrils causing adhesion to this matrix, or aggregate formation induced by ristocetin or by certain lectins also caused an increase in [cyclic-3',5'-GMP]. Contact of platelets either with other platelets or with a matrix therefore results in stimulation of guanylate cyclase. The mechanism responsible for such stimulation remains unclear but does not appear simply to be attributable to activation of nitric oxide synthase by Ca(2+).