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Neuro-psychopharmacological perspective of Orphan receptors of Rhodopsin (class A) family of G protein-coupled receptors

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Abstract

Background

In the central nervous system (CNS), G protein-coupled receptors (GPCRs) are the most fruitful targets for neuropsychopharmacological drug development. Rhodopsin (class A) is the most studied class of GPCR and includes orphan receptors for which the endogenous ligand is not known or is unclear. Characterization of orphan GPCRs has proven to be challenging, and the production pace of GPCR-based drugs has been incredibly slow.

Objective

Determination of the functions of these receptors may provide unexpected insight into physiological and neuropathological processes. Advances in various methods and techniques to investigate orphan receptors including in situ hybridization and knockdown/knockout (KD/KO) showed extensive expression of these receptors in the mammalian brain and unmasked their physiological and neuropathological roles. Due to these rapid progress and development, orphan GPCRs are rising as a new and promising class of drug targets for neurodegenerative diseases and psychiatric disorders.

Conclusion

This review presents a neuropsychopharmacological perspective of 26 orphan receptors of rhodopsin (class A) family, namely GPR3, GPR6, GPR12, GPR17, GPR26, GPR35, GPR39, GPR48, GPR49, GPR50, GPR52, GPR55, GPR61, GPR62, GPR63, GPR68, GPR75, GPR78, GPR83, GPR84, GPR85, GPR88, GPR153, GPR162, GPR171, and TAAR6. We discussed the expression of these receptors in mammalian brain and their physiological roles. Furthermore, we have briefly highlighted their roles in neurodegenerative diseases and psychiatric disorders including Alzheimer’s disease, Parkinson’s disease, neuroinflammation, inflammatory pain, bipolar and schizophrenic disorders, epilepsy, anxiety, and depression.

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Acknowledgments

We gratefully acknowledge the funding from the National 12th Five Year Plan “Major Scientific and Technological Special Project for Significant New Drugs Creation” project of “Novel G protein coupled receptor targeted drug screening system and key technology research” (No. 2012ZX09504001-001) and the Program for New Century Excellent Talents in University (No. NCET-10-0817), which have supported aspects of our research covered in this review. We are highly thankful to Professor Atlas Khan for his expert comments on the manuscript.

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Authors and Affiliations

  1. Department of Pharmacology, China Pharmaceutical University, No. 24 Tong Jia Xiang, Nanjing, Jiangsu Province, 210009, China

    Muhammad Zahid Khan & Ling He

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  1. Muhammad Zahid Khan
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  2. Ling He
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Correspondence to Muhammad Zahid Khan.

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Highlights

• Orphan receptors of rhodopsin (class A) family of GPCR are expressed in the mammalian brain.

• Orphan receptors of rhodopsin (class A) family of GPCR play significant physiological roles in the mammalian brain.

• Orphan receptors of rhodopsin (class A) family of GPCR play significant roles in neurodegenerative diseases and psychiatric disorder including Alzheimer’s disease, Parkinson’s disease, neuroinflammation, inflammatory pain, bipolar and schizophrenic disorders, epilepsy, anxiety, and depression.

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Khan, M.Z., He, L. Neuro-psychopharmacological perspective of Orphan receptors of Rhodopsin (class A) family of G protein-coupled receptors. Psychopharmacology 234, 1181–1207 (2017). https://doi.org/10.1007/s00213-017-4586-9

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  • DOI: https://doi.org/10.1007/s00213-017-4586-9

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