Abstract
Opioid receptors belong to the class A G-protein-coupled receptors and are activated by alkaloid opiates such as morphine, and endogenous ligands such as endorphins and enkephalins. Opioid receptors are widely distributed in the human body and are involved in numerous physiological processes through three major classical opioid receptor subtypes; the mu, delta and kappa along with a lesser characterized subtype, opioid receptor-like (ORL1). Opioids are the most potent analgesics and have been extensively used as a therapeutic drug for the treatment of pain and related disorders. Chronic administration of clinically used opioids is associated with adverse effects such as drug tolerance, addiction and constipation. Several investigations attempted to identify the molecular signaling networks associated with endogenous as well as synthetic opiates, however, there is a paucity of a cumulative depiction of these signaling events. Here, we report a systemic collection of downstream molecules pertaining to four subtypes of opioid receptors (MOR, KOR, DOR and ORL1) in the form of a signaling pathway map. We manually curated reactions induced by the activation of opioid receptors from the literature into five categories- molecular association, activation/inhibition, catalysis, transport, and gene regulation. This led to a dataset of 180 molecules, which is collectively represented in the opioid receptor signaling network following NetPath criteria. We believe that the public availability of an opioid receptor signaling pathway map can accelerate biomedical research in this area because of its high therapeutic significance. The opioid receptors signaling pathway map is uploaded to a freely available web resource, WikiPathways enabling ease of access (https://www.wikipathways.org/index.php/Pathway:WP5093).
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Abbreviations
- DOR:
-
Delta opioid receptor
- MOR:
-
Mu opioid receptor
- KOR:
-
Kappa opioid receptor
- OPRL:
-
Opioid like receptor
- GPCR:
-
G protein-coupled receptor
- DADLE:
-
[D-Ala2, D-Leu5]-Enkephalin
- DALDA:
-
Tyr-D-Arg-Phe-Lys-NH2
- DAMGO:
-
[D-Ala2, N-MePhe4, Gly-ol]-Enkephalin
- OPRD1:
-
δ-Opioid receptor gene
- OPRK1:
-
κ-Opioid receptor gene
- OPRM1:
-
μ-Opioid receptor gene
- PKA:
-
Protein kinase A
- PKC:
-
Protein kinase C
- PTX:
-
Pertussis toxin
- GRK:
-
G Protein-Coupled Receptor Kinase
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Acknowledgements
We thank the Department of Biotechnology, Government of India for research support to the Institute of Bioinformatics, Bangalore. Lathika Gopalakrishnan and Oishi Chatterjee are recipients of Inspire Fellowship from the Department of Science and Technology (DST), Government of India. We thank Karnataka Biotechnology and Information Technology Services (KBITS), Government of Karnataka for the support to the Center for Systems Biology and Molecular Medicine at Yenepoya (Deemed to be University) under the Biotechnology Skill Enhancement Programme in Multiomics Technology (BiSEP GO ITD 02 MDA 2017). Rajesh Raju is a recipient of the Young Scientist Award (YSS/2014/000607) from the Science and Engineering Research Board, Department of Science and Technology (DST), Government of India.
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Gopalakrishnan, L., Chatterjee, O., Ravishankar, N. et al. Opioid receptors signaling network. J. Cell Commun. Signal. 16, 475–483 (2022). https://doi.org/10.1007/s12079-021-00653-z
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DOI: https://doi.org/10.1007/s12079-021-00653-z