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Smith NJ. Drug Discovery Opportunities at the Endothelin B Receptor-Related Orphan G Protein-Coupled Receptors, GPR37 and GPR37L1. Front Pharmacol. 2015;6:275doi: 10.3389/fphar.2015.00275.
Smith, N. J. (2015). Drug Discovery Opportunities at the Endothelin B Receptor-Related Orphan G Protein-Coupled Receptors, GPR37 and GPR37L1. Frontiers in pharmacology, 6275. https://doi.org/10.3389/fphar.2015.00275
Smith, Nicola J. "Drug Discovery Opportunities at the Endothelin B Receptor-Related Orphan G Protein-Coupled Receptors, GPR37 and GPR37L1." Frontiers in pharmacology vol. 6 (2015): 275. doi: https://doi.org/10.3389/fphar.2015.00275
Smith NJ. Drug Discovery Opportunities at the Endothelin B Receptor-Related Orphan G Protein-Coupled Receptors, GPR37 and GPR37L1. Front Pharmacol. 2015 Nov 17;6:275. doi: 10.3389/fphar.2015.00275. eCollection 2015. PMID: 26635605; PMCID: PMC4648071.
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Front Pharmacol. 2015 Nov 17;6:275. doi: 10.3389/fphar.2015.00275. eCollection 2015.

Drug Discovery Opportunities at the Endothelin B Receptor-Related Orphan G Protein-Coupled Receptors, GPR37 and GPR37L1.

Frontiers in pharmacology

Nicola J Smith

Affiliations

  1. Molecular Cardiology Program, Victor Chang Cardiac Research Institute , Darlinghurst, NSW, Australia ; St. Vincent's Clinical School, University of New South Wales , Darlinghurst, NSW, Australia.

PMID: 26635605 PMCID: PMC4648071 DOI: 10.3389/fphar.2015.00275

Abstract

Orphan G protein-coupled receptors (GPCRs) represent a largely untapped resource for the treatment of a variety of diseases, despite sophisticated advances in drug discovery. Two promising orphan GPCRs are the endothelin B receptor-like proteins, GPR37 [ET(B)R-LP, Pael-R] and GPR37L1 [ET(B)R-LP-2]. Originally identified through searches for homologs of endothelin and bombesin receptors, neither GPR37 nor GPR37L1 were found to bind endothelins or related peptides. Instead, GPR37 was proposed to be activated by head activator (HA) and both GPR37 and GPR37L1 have been linked to the neuropeptides prosaposin and prosaptide, although these pairings are yet to be universally acknowledged. Both orphan GPCRs are widely expressed in the brain, where GPR37 has received the most attention for its link to Parkinson's disease and parkinsonism, while GPR37L1 deletion leads to precocious cerebellar development and hypertension. In this review, the existing pharmacology and physiology of GPR37 and GPR37L1 is discussed and the potential therapeutic benefits of targeting these receptors are explored.

Keywords: ETB; G protein-coupled receptor; GPR37; GPR37L1; Pael-R; endothelin; orphan; parkin

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