Portal de Periódicos da CAPES

Chapter 20. Platelet-Activating Factor: Multifaceted Biochemical and Physiological Mediator

1985; Elsevier BV; Linguagem: Inglês

10.1016/s0065-7743(08)61046-5

1557-8437

Michael C. Venuti,

Cytokine Signaling Pathways and Interactions

This chapter discusses the characteristics and the role of platelet-activating factor (PAF) as a multifaceted biochemical and physiological mediator. Procedures for both semi-synthesis and total synthesis of PAF on a sufficiently large scale for biochemical investigations have been refined and improved. Reported successes in the search for specific receptor antagonists of PAF action can be divided into two categories. The first group is comprised of lipids possessing a thiazolium polar head group. A second group is comprised of two natural products, kadsurenone and ginkgolide-B, structurally unrelated to PAF. Detailed examination of the release of PAF from a variety of cell types, utilizing a number of stimuli, has provided new information regarding the two biosynthetic pathways for the production of PAF. The most recent development in PAF biosynthesis has provided a surprising link between PAF itself and the arachidonate metabolites. The structural requirements for and the existence of antagonists of the PAF activity both directly point to the presence of specific PAF cell membrane receptors in platelets. Although PAF is a potent platelet-aggregating agent, detailed investigations of the pathophysiological manifestations of the effects of PAF have focused attention on its role as a key anaphylactomimetic mediator. The hypotensive activity of PAF, one of the first noted and the most pronounced pharmacological property, observable in the rat, whose platelets are refractory to PAF. The still expanding range of biological activities, exhibited by PAF, coupled with the variety of cell types that produce PAF, firmly established it as a key mediator of the inflammatory and anaphylactic events. While it is unlikely that PAF itself is solely responsible for the pathogenesis of acute and allergic inflammation, it is quite apparent that PAF must be included among the important mediators of normal and abnormal acute allergic and inflammatory reactions.