Eicosanoids as Second Messengers

Several additional intracellular actions have been described for the eicosanoids, including the regulation of the multifunctional protein kinase, PKC, of ion pumps such as the Na /K ATPase, and of a variety of membrane ion channels in excitable cells from 

The superfamily of nuclear receptor proteins is constituted by a group of transcription factors that are activated, in most cases, by hormonal ligands. For example, steroid hormones, thyroid hormones and retinoic acid bind selectively to receptors that belong to this superfamily. The hormone-receptor complexes interact with m-act-ing elements present on the promoter sequences of target genes, initiating a series of transcription events that are responsible for the hormone s effects.  

How does PPARy produce these responses Like other members of the nuclear receptor superfamily, PPARy contains a DNA-binding domain that recognizes hormone-responsive elements in the promoter regions of its target genes. Before binding to these sequences, however, PPARy must first combine with the 9-c/V-retinoic acid receptor, forming an active heterodimer (Fig. 5.2).  

The possibility that PPARy participates in normal and pathological adipocyte differentiation has aroused considerable interest and has prompted an active search for endogenous molecules that may serve as ligands for this nuclear receptor. Along with drugs 

In one of these studies, at least 10 different prostanoids were compared for their ability to activate PPARy in CV1 cells, a cell line that expresses this receptor constitutively. PGD2 and its two metabolites, PGJ2 and A -PGJ2, activated PPARy by approximately 4-fold. Most effective in this respect was, however, a third PGD2 metabolite, 15-deoxy-A -PGj2, which caused a 14-fold enhancement in 

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