Isolation and properties of platelet-activating factor receptor cDNAs.

The cDNA encoding the platelet-activating factor (PAF) receptor was cloned from a guinea pig lung cDNA library by using a Xenopus laevis oocyte expression system. The human PAF receptor cDNA was isolated from a human leukocyte cDNA library using a 0.8-kbp fragment of the guinea pig PAF receptor cDNA as a probe. Both receptors have the same number of amino acids (342 residues) with seven putative transmembrane spanning domains, and belong to the G-protein-linked receptor superfamily. Overall amino acid identity between the two receptors was 83%:91% in the transmembrane domains. Seven threonine and three serine residues conserved in the cytoplasmic loops of both receptors may function as phosphate acceptors, as related to the homologous desensitization of the receptor. Activation of the PAF receptor yielded inositol 1,4,5-trisphosphate production in the PAF receptor expressed COS-7 cells and oocytes, and guanosine 5'-O-(2-thio)bisphosphate injected into the oocytes inhibited PAF-induced Cl- current, providing evidence that PAF stimulates phosphoinositide turnover via G-protein(s).