Receptor structural diversity

Figure 11.6 Schematic representation of the GABAa receptor complex. Examples of the many structurally diverse compounds that act at different sites on the receptor (see text for details). Picrotoxinin, the active component of picrotoxin, and TBPS act as non-competitive antagonists. The barbiturates, steroids and anaesthetics are positive allosteric modulators, as are the benzodiazepine site ligands shown, with the exception of DMCM (negative allosteric modulator) and flumazenil (benzodiazepine site antagonist)...

Waxman DJ. P450 gene induction by structurally diverse xenochemicals central role of nuclear receptors CAR, PXR, and PPAR1. Arch Biochem Biophys 1999 369 11-23. 

The most important molecules so far identified from this screen include a likely transduction channel, an extracellular molecule that could gate channels, and several molecules known to be important for axonemal structure and function. Although the set of molecules is less complete than that identified for C. elegans touch receptors, the diversity of mechanotransduction in Drosophila and the apparent similarity of these receptors to those in vertebrates, including hair cells (see below), demonstrates the significance of this model system. 

There are a variety of structural classes of compounds that are active against each phosphodiesterase, and evidence suggests that selective inhibitors of PDEs can be identified. The structural diversity of PDE inhibitors provides a multitude of opportunities for development of compounds with drug-like properties. Furthermore, phosphodiesterase inhibition, which avoids direct interaction of a compound with a cell surface or nuclear receptor, may circumvent some of the target selectivity issues that can complicate receptor-based therapeutic approaches. As noted above, the specific subcellular distribution of phosphodiesterase enzymes is a key feature of their ability to modulate intracellular signaling pathways. This localization of the enzyme may minimize non-specific target... 

The structural diversity associated with bicyclic 5-5 fused heterocyclic systems containing two heteroatoms in each ring has been noted previously in both CHEC(1984) <1984CHEC(6)1027> and CHEC-II(1996) <1996CHEC-11(7)115>. In recent years this diversity has also been reflected in the number of applications that have been found for these compounds which include organic metals, molecular clips and receptors and molecular magnets. These fields will be examined in due course through this chapter. 

D. Larhammar (1996). Structural diversity of receptors for neuropeptide Y, peptide YY and pancreatic polypeptide. Regul. Pept. 65 165. 

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