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The biological functions of platelet-activating factor (PAF) have been extensively studied in the rat. However, the precise structure and distribution of rat PAF receptor has not been reported. To address this question, we isolated a rat PAF-receptor cDNA from a size-fractionated rat spleen cDNA library. The deduced amino acid sequence of the rat PAF receptor showed 80% and 79% identity with guinea pig and human PAF receptors, respectively. Pharmacological properties (ED50, inhibition by WEB2086) of rat PAF receptors expressed in Xenopus oocytes were similar to those for PAF receptors expressed from guinea pig or human cDNAs. Northern blot analysis showed a widespread distribution of PAF-receptor mRNA in almost all organs including spleen, small intestine, kidney, lung, liver and brain. Considerable difference in the PAF-receptor distribution detected among species suggests the existence of a species-specific and tissue-specific regulatory mechanism for PAF-receptor-mRNA expression. Isolation of rat PAF-receptor cDNA should facilitate further analysis of PAF-receptor function and pharmacology in diverse pathophysiological processes.