Pharmacological diversity of GPCRs

In the post-genome (proteome) era long established views of receptor pharmacology are changing since modifications of GPCR structure and function can contribute to the pharmacological diversity found for products of a single GPCR gene. The changes in GPCR structure and function can occur at different levels. For example, gene duplication events that have led to multiple receptor subtypes are the cause of a considerable functional diversity found in one transmitter system. Moreover, tissue-specific splicing, RNA editing, and variations in post-translational modifications can multiply the products derived from a single GPCR gene (Fig. 1.2 and also see Chapter 2). In addition, tissue- or cell-specific expression of effectors can modify the ligand preference and signal transduction capabilities of GPCRs, so

Genomic level Family Group (subfamily) Subgroup Subtype, pseudogene

Transcriptional level

Splice variants RNA editing

Protein level Protein folding Post-translational modification Receptor sorting Homo-, heterodimers Co-receptors Dominant effects

Functional level Multiple coupling Basal activity Co-factors

Fig. 1.2 Molecular basis of the functional diversity of GPCRs. Functional diversity of GPCRs is determined at different levels. The molecular mechanisms underlying this phenomenon include gene duplication, RNA and post-translational modifications as well as interaction with various co-factors and other GPCR molecules.

that specificity and function of a given GPCR can vary when expressed in a different cellular environment (Chapter 7).

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