CLONING BY FUNCTIONAL EXPRESSION OF PLATELET-ACTIVATING-FACTOR RECEPTOR FROM GUINEA-PIG LUNG

PLATELET-activating factor (PAF), a unique phospholipid mediator, possesses potent proinflammatory, smooth-muscle contractile and hypotensive activities, and appears to be crucial in the pathogenesis of bronchial asthma and in the lethality of endotoxin and anaphylactic shock1-3. Despite this, little is known of the molecular properties of the PAF receptor and related signal transduction systems. Although several lines of evidence suggest that activation of the PAF receptor stimulates phospholipase C and subsequent inositol trisphosphate formation through G protein(s)4,5, the PAF receptor and calcium channel are reported to show a close relation2,6. As a first approach to cloning lipid autacoid receptors, we have isolated complementary DNA for the PAF receptors. Our strategy involved gene expression in Xenopus laevis oocytes and electrophysiological detection of PAF-induced responses. Sequence analysis indicates that the receptor belongs to the superfamily of G protein-coupled receptors.