Platelet Activating Factor Receptors
2003
Platelet activating factor (PAF) is a potent pro-inflammatory lipid mediator. Its effects are mediated through cell surface G protein-coupled receptors (GPCRs) that are distributed on numerous cells notably on endothelium [1]. An intracrine mode of action for PAF is proposed based on evidence for intracellular PAF binding sites [2] and retention of newly generated PAF within its producing cells [3]. Separate functions for the intracellular and cell surface receptors are suggested using agents which putatively distinguish them [4, 5]; immediate effects are mediated by cell surface receptors whereas regulation of gene expression are dependent upon intracellular receptors consistent with presence of signaling effectors in nuclei including G proteins, Ca++, kinases and NF-κB [6,6,8]; but intracellular PAF receptors; especially on nuclei, which may explain their presumed involvement in gene regulation [5] has never been explicitly demonstrated. We speculated that PAF receptors exist at the cell nucleus where they induce major pro-inflammatory gene cyclooxygenase-2 (COX-2) expression.
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