Prostaglandin endoperoxides and thromboxane A₂ can induce platelet aggregation in the absence of secretion

Abstract

PLATELET aggregation and secretion are widely studied not only because they are believed to reflect the major in vivo platelet function, formation of the primary haemostatic plug, but also because they involve fundamental cellular regulatory mechanisms. The synthesis of biologically active prostaglandin (PG) intermediates (endoperoxides and thromboxanes) seems to be an important step in the regulation of platelet function^1,2, but the physiological roles and mechanism(s) of these compounds are unknown. It is claimed by Malmsten et al.³ and Samuelsson et. al.⁴ that PG endoperoxides and thromboxane A₂ cause platelet aggregation only by inducing platelets to secrete ADP that in turn causes aggregation. In view of observations that platelets deficient in releasable ADP (storage pool-deficient platelets or platelets depleted of storage granules) still aggregate in response to arachidonic acid^5–7, the precursor of the intermediates, the validity of this claim has been open to question. We have investigated platelet stimulation by PG endoperoxides (PGG₂ and PGH₂), an endoperoxide analogue ((15S)-hydroxy-11α, 9α-(epoxymethano) prosta-5Z, 13E-dienoic acid; U-46619), thromboxane A₂-like material and arachidonic acid, using a new instrument that simultaneously monitors aggregation and secretion in the same platelet suspension⁸, permitting careful analysis of the relationships between aggregation and secretion. We report here that although high concentrations of the endoperoxide analogue, the natural endoperoxides and thromboxane A₂ induce both platelet aggregation and secretion, low concentrations cause aggregation without detectable secretion.