G Protein-Coupled Receptor (GPCR) Expression in Native Cells: "Novel" endoGPCRs as Physiologic Regulators and Therapeutic Targets

Paul A Insel, Andrea Wilderman, Alexander C Zambon, Aaron N Snead, Fiona Murray, Nakon Aroonsakool, Daniel S McDonald, Shu Zhou, Thalia McCann, Lingzhi Zhang, Krishna Sriram, Amy M Chinn, Alexander V Michkov, Rebecca M Lynch, Aaron C Overland, Ross Corriden

Research output: Contribution to journalArticle

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Abstract

G protein-coupled receptors (GPCRs), the largest family of signaling receptors in the human genome, are also the largest class of targets of approved drugs. Are the optimal GPCRs (in terms of efficacy and safety) currently targeted therapeutically? Especially given the large number (∼ 120) of orphan GPCRs (which lack known physiologic agonists), it is likely that previously unrecognized GPCRs, especially orphan receptors, regulate cell function and can be therapeutic targets. Knowledge is limited regarding the diversity and identity of GPCRs that are activated by endogenous ligands and that native cells express. Here, we review approaches to define GPCR expression in tissues and cells and results from studies using these approaches. We identify problems with the available data and suggest future ways to identify and validate the physiologic and therapeutic roles of previously unrecognized GPCRs. We propose that a particularly useful approach to identify functionally important GPCRs with therapeutic potential will be to focus on receptors that show selective increases in expression in diseased cells from patients and experimental animals.

Original languageEnglish
Pages (from-to)181-187
Number of pages7
JournalMolecular Pharmacology
Volume88
Issue number1
DOIs
Publication statusPublished - Jul 2015

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G-Protein-Coupled Receptors
Therapeutics
Orphaned Children
Human Genome
Ligands
Safety
Pharmaceutical Preparations

Keywords

  • Animals
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Humans
  • Molecular Targeted Therapy
  • Receptors, G-Protein-Coupled
  • Tissue Distribution

Cite this

G Protein-Coupled Receptor (GPCR) Expression in Native Cells: "Novel" endoGPCRs as Physiologic Regulators and Therapeutic Targets. / Insel, Paul A; Wilderman, Andrea; Zambon, Alexander C; Snead, Aaron N; Murray, Fiona; Aroonsakool, Nakon; McDonald, Daniel S; Zhou, Shu; McCann, Thalia; Zhang, Lingzhi; Sriram, Krishna; Chinn, Amy M; Michkov, Alexander V; Lynch, Rebecca M; Overland, Aaron C; Corriden, Ross.

In: Molecular Pharmacology, Vol. 88, No. 1, 07.2015, p. 181-187.

Research output: Contribution to journalArticle

Insel, PA, Wilderman, A, Zambon, AC, Snead, AN, Murray, F, Aroonsakool, N, McDonald, DS, Zhou, S, McCann, T, Zhang, L, Sriram, K, Chinn, AM, Michkov, AV, Lynch, RM, Overland, AC & Corriden, R 2015, 'G Protein-Coupled Receptor (GPCR) Expression in Native Cells: "Novel" endoGPCRs as Physiologic Regulators and Therapeutic Targets', Molecular Pharmacology, vol. 88, no. 1, pp. 181-187. https://doi.org/10.1124/mol.115.098129
Insel, Paul A ; Wilderman, Andrea ; Zambon, Alexander C ; Snead, Aaron N ; Murray, Fiona ; Aroonsakool, Nakon ; McDonald, Daniel S ; Zhou, Shu ; McCann, Thalia ; Zhang, Lingzhi ; Sriram, Krishna ; Chinn, Amy M ; Michkov, Alexander V ; Lynch, Rebecca M ; Overland, Aaron C ; Corriden, Ross. / G Protein-Coupled Receptor (GPCR) Expression in Native Cells: "Novel" endoGPCRs as Physiologic Regulators and Therapeutic Targets. In: Molecular Pharmacology. 2015 ; Vol. 88, No. 1. pp. 181-187.
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abstract = "G protein-coupled receptors (GPCRs), the largest family of signaling receptors in the human genome, are also the largest class of targets of approved drugs. Are the optimal GPCRs (in terms of efficacy and safety) currently targeted therapeutically? Especially given the large number (∼ 120) of orphan GPCRs (which lack known physiologic agonists), it is likely that previously unrecognized GPCRs, especially orphan receptors, regulate cell function and can be therapeutic targets. Knowledge is limited regarding the diversity and identity of GPCRs that are activated by endogenous ligands and that native cells express. Here, we review approaches to define GPCR expression in tissues and cells and results from studies using these approaches. We identify problems with the available data and suggest future ways to identify and validate the physiologic and therapeutic roles of previously unrecognized GPCRs. We propose that a particularly useful approach to identify functionally important GPCRs with therapeutic potential will be to focus on receptors that show selective increases in expression in diseased cells from patients and experimental animals.",
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