Retinoids in Transmembrane Signaling

2 Retinoids in Transmembrane Signaling Neutrophils treated with physiological concentrations of all-tra s-retinoic acid show a dose-dependent increase in synthesis of superoxide. Inhibitor studies suggest that retinoic acid acts via an inositol trisphosphate cascade rather than calcium and protein kinase C (Koga et al., 1997). There is also evidence that all-rrans-retinoic acid leads to increased formation of cADP-ribose and nicotinic acid adenine dinucleotide phosphate as second messengers (Section 8.4.4 Dousa et al., 1996 Mehta and Cheema, 1999). 

Some of the retroretinoids also have cell signaling functions at a cell surface or a cytoplasmic receptor. 14-Hydroxyretroretinol is required for lymphocyte proliferation, whereas anhydroretinol is a growth inhibitor the two compounds act antagonistically. Treatment of T lymphocytes with anhydroretinol in the absence of 14-hydroxyretroretinol leads to rapid cell death. 

There is also evidence that retinoic acid directly modulates transmission at electrical synapses of retinal cells. This is independent of G-proteins and second messengers, and involves a nonnuclear RAR-like binding site associated with ion channels (Zhang and McMahon, 2000). 

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