7ul5

Structural highlights

Function

OPRK_HUMAN G-protein coupled opioid receptor that functions as receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. Also functions as receptor for various synthetic opioids and for the psychoactive diterpene salvinorin A. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain. Plays a role in mediating reduced physical activity upon treatment with synthetic opioids. Plays a role in the regulation of salivation in response to synthetic opioids. May play a role in arousal and regulation of autonomic and neuroendocrine functions.^{[1] [2] [3] [4]} SSR2_HUMAN Receptor for somatostatin-14 and -28. This receptor is coupled via pertussis toxin sensitive G proteins to inhibition of adenylyl cyclase. In addition it stimulates phosphotyrosine phosphatase and PLC via pertussis toxin insensitive as well as sensitive G proteins. Inhibits calcium entry by suppressing voltage-dependent calcium channels. Acts as the functionally dominant somatostatin receptor in pancreatic alpha- and beta-cells where it mediates the inhibitory effect of somatostatin-14 on hormone secretion. Inhibits cell growth through enhancement of MAPK1 and MAPK2 phosphorylation and subsequent up-regulation of CDKN1B. Stimulates neuronal migration and axon outgrowth and may participate in neuron development and maturation during brain development. Mediates negative regulation of insulin receptor signaling through PTPN6. Inactivates SSTR3 receptor function following heterodimerization.^{[5] [6] [7] [8] [9]}

References

1. ↑ Li JG, Chen C, Liu-Chen LY. Ezrin-radixin-moesin-binding phosphoprotein-50/Na+/H+ exchanger regulatory factor (EBP50/NHERF) blocks U50,488H-induced down-regulation of the human kappa opioid receptor by enhancing its recycling rate. J Biol Chem. 2002 Jul 26;277(30):27545-52. Epub 2002 May 9. PMID:12004055 doi:http://dx.doi.org/10.1074/jbc.M200058200
2. ↑ Wu H, Wacker D, Mileni M, Katritch V, Han GW, Vardy E, Liu W, Thompson AA, Huang XP, Carroll FI, Mascarella SW, Westkaemper RB, Mosier PD, Roth BL, Cherezov V, Stevens RC. Structure of the human kappa-opioid receptor in complex with JDTic. Nature. 2012 Mar 21;485(7398):327-32. doi: 10.1038/nature10939. PMID:22437504 doi:10.1038/nature10939
3. ↑ Simonin F, Gaveriaux-Ruff C, Befort K, Matthes H, Lannes B, Micheletti G, Mattei MG, Charron G, Bloch B, Kieffer B. kappa-Opioid receptor in humans: cDNA and genomic cloning, chromosomal assignment, functional expression, pharmacology, and expression pattern in the central nervous system. Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):7006-10. PMID:7624359
4. ↑ Mansson E, Bare L, Yang D. Isolation of a human kappa opioid receptor cDNA from placenta. Biochem Biophys Res Commun. 1994 Aug 15;202(3):1431-7. PMID:8060324
5. ↑ Grant M, Collier B, Kumar U. Agonist-dependent dissociation of human somatostatin receptor 2 dimers: a role in receptor trafficking. J Biol Chem. 2004 Aug 27;279(35):36179-83. doi: 10.1074/jbc.M407310200. Epub 2004, Jul 1. PMID:15231824 doi:http://dx.doi.org/10.1074/jbc.M407310200
6. ↑ Grant M, Alturaihi H, Jaquet P, Collier B, Kumar U. Cell growth inhibition and functioning of human somatostatin receptor type 2 are modulated by receptor heterodimerization. Mol Endocrinol. 2008 Oct;22(10):2278-92. doi: 10.1210/me.2007-0334. Epub 2008 Jul, 24. PMID:18653781 doi:http://dx.doi.org/10.1210/me.2007-0334
7. ↑ Le Verche V, Kaindl AM, Verney C, Csaba Z, Peineau S, Olivier P, Adle-Biassette H, Leterrier C, Vitalis T, Renaud J, Dargent B, Gressens P, Dournaud P. The somatostatin 2A receptor is enriched in migrating neurons during rat and human brain development and stimulates migration and axonal outgrowth. PLoS One. 2009;4(5):e5509. doi: 10.1371/journal.pone.0005509. Epub 2009 May 12. PMID:19434240 doi:http://dx.doi.org/10.1371/journal.pone.0005509
8. ↑ Parry JJ, Chen R, Andrews R, Lears KA, Rogers BE. Identification of critical residues involved in ligand binding and G protein signaling in human somatostatin receptor subtype 2. Endocrinology. 2012 Jun;153(6):2747-55. doi: 10.1210/en.2011-1662. Epub 2012 Apr , 11. PMID:22495673 doi:http://dx.doi.org/10.1210/en.2011-1662
9. ↑ Kailey B, van de Bunt M, Cheley S, Johnson PR, MacDonald PE, Gloyn AL, Rorsman P, Braun M. SSTR2 is the functionally dominant somatostatin receptor in human pancreatic beta- and alpha-cells. Am J Physiol Endocrinol Metab. 2012 Nov 1;303(9):E1107-16. doi:, 10.1152/ajpendo.00207.2012. Epub 2012 Aug 28. PMID:22932785 doi:http://dx.doi.org/10.1152/ajpendo.00207.2012