NameMu-type opioid receptor
Synonyms
  • hMOP
  • M-OR-1
  • MOP
  • MOR1
  • Mu opiate receptor
  • Mu opioid receptor
Gene NameOPRM1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0001536|Mu-type opioid receptor
MDSSAAPTNASNCTDALAYSSCSPAPSPGSWVNLSHLDGNLSDPCGPNRTDLGGRDSLCP
PTGSPSMITAITIMALYSIVCVVGLFGNFLVMYVIVRYTKMKTATNIYIFNLALADALAT
STLPFQSVNYLMGTWPFGTILCKIVISIDYYNMFTSIFTLCTMSVDRYIAVCHPVKALDF
RTPRNAKIINVCNWILSSAIGLPVMFMATTKYRQGSIDCTLTFSHPTWYWENLLKICVFI
FAFIMPVLIITVCYGLMILRLKSVRMLSGSKEKDRNLRRITRMVLVVVAVFIVCWTPIHI
YVIIKALVTIPETTFQTVSWHFCIALGYTNSCLNPVLYAFLDENFKRCFREFCIPTSSNI
EQQNSTRIRQNTRDHPSTANTVDRTNHQLENLEAETAPLP
Number of residues400
Molecular Weight44778.855
Theoretical pI8.29
GO Classification
Functions
  • G-protein alpha-subunit binding
  • G-protein beta-subunit binding
  • voltage-gated calcium channel activity
  • G-protein coupled receptor activity
  • beta-endorphin receptor activity
  • morphine receptor activity
  • neuropeptide binding
Processes
  • opioid receptor signaling pathway
  • positive regulation of nitric oxide biosynthetic process
  • negative regulation of cell proliferation
  • regulation of N-methyl-D-aspartate selective glutamate receptor activity
  • phospholipase C-activating G-protein coupled receptor signaling pathway
  • locomotory behavior
  • negative regulation of nitric oxide biosynthetic process
  • G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
  • positive regulation of neurogenesis
  • sensory perception of pain
  • negative regulation of cAMP-mediated signaling
  • adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway
  • calcium ion transmembrane transport
  • cellular response to stress
  • adenylate cyclase-activating dopamine receptor signaling pathway
  • negative regulation of adenylate cyclase activity
  • neuropeptide signaling pathway
  • positive regulation of ERK1 and ERK2 cascade
  • synaptic transmission
  • cellular response to morphine
  • positive regulation of cAMP-mediated signaling
  • sensory perception
  • negative regulation of Wnt protein secretion
  • negative regulation of cytosolic calcium ion concentration
  • behavioral response to ethanol
  • positive regulation of cytosolic calcium ion concentration
Components
  • integral component of plasma membrane
  • neuron projection
  • endoplasmic reticulum
  • plasma membrane
  • Golgi apparatus
  • cytosol
General FunctionVoltage-gated calcium channel activity
Specific FunctionReceptor for endogenous opioids such as beta-endorphin and endomorphin. Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone. Agonist binding to the receptor induces coupling to an inactive GDP-bound heterotrimeric G-protein complex and subsequent exchange of GDP for GTP in the G-protein alpha subunit leading to dissociation of the G-protein complex with the free GTP-bound G-protein alpha and the G-protein beta-gamma dimer activating downstream cellular effectors. The agonist- and cell type-specific activity is predominantly coupled to pertussis toxin-sensitive G(i) and G(o) G alpha proteins, GNAI1, GNAI2, GNAI3 and GNAO1 isoforms Alpha-1 and Alpha-2, and to a lesser extend to pertussis toxin-insensitive G alpha proteins GNAZ and GNA15. They mediate an array of downstream cellular responses, including inhibition of adenylate cyclase activity and both N-type and L-type calcium channels, activation of inward rectifying potassium channels, mitogen-activated protein kinase (MAPK), phospholipase C (PLC), phosphoinositide/protein kinase (PKC), phosphoinositide 3-kinase (PI3K) and regulation of NF-kappa-B. Also couples to adenylate cyclase stimulatory G alpha proteins. The selective temporal coupling to G-proteins and subsequent signaling can be regulated by RGSZ proteins, such as RGS9, RGS17 and RGS4. Phosphorylation by members of the GPRK subfamily of Ser/Thr protein kinases and association with beta-arrestins is involved in short-term receptor desensitization. Beta-arrestins associate with the GPRK-phosphorylated receptor and uncouple it from the G-protein thus terminating signal transduction. The phosphorylated receptor is internalized through endocytosis via clathrin-coated pits which involves beta-arrestins. The activation of the ERK pathway occurs either in a G-protein-dependent or a beta-arrestin-dependent manner and is regulated by agonist-specific receptor phosphorylation. Acts as a class A G-protein coupled receptor (GPCR) which dissociates from beta-arrestin at or near the plasma membrane and undergoes rapid recycling. Receptor down-regulation pathways are varying with the agonist and occur dependent or independent of G-protein coupling. Endogenous ligands induce rapid desensitization, endocytosis and recycling whereas morphine induces only low desensitization and endocytosis. Heterooligomerization with other GPCRs can modulate agonist binding, signaling and trafficking properties. Involved in neurogenesis. Isoform 12 couples to GNAS and is proposed to be involved in excitatory effects. Isoform 16 and isoform 17 do not bind agonists but may act through oligomerization with binding-competent OPRM1 isoforms and reduce their ligand binding activity.
Pfam Domain Function
Transmembrane Regions69-93 107-131 143-165 186-207 231-255 284-307 315-338
GenBank Protein ID452073
UniProtKB IDP35372
UniProtKB Entry NameOPRM_HUMAN
Cellular LocationCell membrane
Gene sequence
>lcl|BSEQ0021649|Mu-type opioid receptor (OPRM1)
ATGGACAGCAGCGCTGCCCCCACGAACGCCAGCAATTGCACTGATGCCTTGGCGTACTCA
AGTTGCTCCCCAGCACCCAGCCCCGGTTCCTGGGTCAACTTGTCCCACTTAGATGGCAAC
CTGTCCGACCCATGCGGTCCGAACCGCACCGACCTGGGCGGGAGAGACAGCCTGTGCCCT
CCGACCGGCAGTCCCTCCATGATCACGGCCATCACGATCATGGCCCTCTACTCCATCGTG
TGCGTGGTGGGGCTCTTCGGAAACTTCCTGGTCATGTATGTGATTGTCAGATACACCAAG
ATGAAGACTGCCACCAACATCTACATTTTCAACCTTGCTCTGGCAGATGCCTTAGCCACC
AGTACCCTGCCCTTCCAGAGTGTGAATTACCTAATGGGAACATGGCCATTTGGAACCATC
CTTTGCAAGATAGTGATCTCCATAGATTACTATAACATGTTCACCAGCATATTCACCCTC
TGCACCATGAGTGTTGATCGATACATTGCAGTCTGCCACCCTGTCAAGGCCTTAGATTTC
CGTACTCCCCGAAATGCCAAAATTATCAATGTCTGCAACTGGATCCTCTCTTCAGCCATT
GGTCTTCCTGTAATGTTCATGGCTACAACAAAATACAGGCAAGGTTCCATAGATTGTACA
CTAACATTCTCTCATCCAACCTGGTACTGGGAAAACCTGCTGAAGATCTGTGTTTTCATC
TTCGCCTTCATTATGCCAGTGCTCATCATTACCGTGTGCTATGGACTGATGATCTTGCGC
CTCAAGAGTGTCCGCATGCTCTCTGGCTCCAAAGAAAAGGACAGGAATCTTCGAAGGATC
ACCAGGATGGTGCTGGTGGTGGTGGCTGTGTTCATCGTCTGCTGGACTCCCATTCACATT
TACGTCATCATTAAAGCCTTGGTTACAATCCCAGAAACTACGTTCCAGACTGTTTCTTGG
CACTTCTGCATTGCTCTAGGTTACACAAACAGCTGCCTCAACCCAGTCCTTTATGCATTT
CTGGATGAAAACTTCAAACGATGCTTCAGAGAGTTCTGTATCCCAACCTCTTCCAACATT
GAGCAACAAAACTCCACTCGAATTCGTCAGAACACTAGAGACCACCCCTCCACGGCCAAT
ACAGTGGATAGAACTAATCATCAGCTAGAAAATCTGGAAGCAGAAACTGCTCCGTTGCCC
TAA
GenBank Gene IDL25119
GeneCard IDNot Available
GenAtlas IDOPRM1
HGNC IDHGNC:8156
Chromosome Location6
Locus6q24-q25
References
  1. Wang JB, Johnson PS, Persico AM, Hawkins AL, Griffin CA, Uhl GR: Human mu opiate receptor. cDNA and genomic clones, pharmacologic characterization and chromosomal assignment. FEBS Lett. 1994 Jan 31;338(2):217-22. 7905839
  2. Bare LA, Mansson E, Yang D: Expression of two variants of the human mu opioid receptor mRNA in SK-N-SH cells and human brain. FEBS Lett. 1994 Nov 7;354(2):213-6. 7957926
  3. Mestek A, Hurley JH, Bye LS, Campbell AD, Chen Y, Tian M, Liu J, Schulman H, Yu L: The human mu opioid receptor: modulation of functional desensitization by calcium/calmodulin-dependent protein kinase and protein kinase C. J Neurosci. 1995 Mar;15(3 Pt 2):2396-406. 7891175
  4. Pan YX, Xu J, Mahurter L, Xu M, Gilbert AK, Pasternak GW: Identification and characterization of two new human mu opioid receptor splice variants, hMOR-1O and hMOR-1X. Biochem Biophys Res Commun. 2003 Feb 21;301(4):1057-61. 12589820
  5. Cadet P, Mantione KJ, Stefano GB: Molecular identification and functional expression of mu 3, a novel alternatively spliced variant of the human mu opiate receptor gene. J Immunol. 2003 May 15;170(10):5118-23. 12734358
  6. Pan L, Xu J, Yu R, Xu MM, Pan YX, Pasternak GW: Identification and characterization of six new alternatively spliced variants of the human mu opioid receptor gene, Oprm. Neuroscience. 2005;133(1):209-20. 15893644
  7. Xu J, Xu M, Hurd YL, Pasternak GW, Pan YX: Isolation and characterization of new exon 11-associated N-terminal splice variants of the human mu opioid receptor gene. J Neurochem. 2009 Feb;108(4):962-72. doi: 10.1111/j.1471-4159.2008.05833.x. Epub 2008 Dec 10. 19077058
  8. Shabalina SA, Zaykin DV, Gris P, Ogurtsov AY, Gauthier J, Shibata K, Tchivileva IE, Belfer I, Mishra B, Kiselycznyk C, Wallace MR, Staud R, Spiridonov NA, Max MB, Goldman D, Fillingim RB, Maixner W, Diatchenko L: Expansion of the human mu-opioid receptor gene architecture: novel functional variants. Hum Mol Genet. 2009 Mar 15;18(6):1037-51. doi: 10.1093/hmg/ddn439. Epub 2008 Dec 22. 19103668
  9. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  10. Mungall AJ, Palmer SA, Sims SK, Edwards CA, Ashurst JL, Wilming L, Jones MC, Horton R, Hunt SE, Scott CE, Gilbert JG, Clamp ME, Bethel G, Milne S, Ainscough R, Almeida JP, Ambrose KD, Andrews TD, Ashwell RI, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beare DM, Beasley H, Beasley O, Bird CP, Blakey S, Bray-Allen S, Brook J, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Clark SY, Clark G, Clee CM, Clegg S, Cobley V, Collier RE, Collins JE, Colman LK, Corby NR, Coville GJ, Culley KM, Dhami P, Davies J, Dunn M, Earthrowl ME, Ellington AE, Evans KA, Faulkner L, Francis MD, Frankish A, Frankland J, French L, Garner P, Garnett J, Ghori MJ, Gilby LM, Gillson CJ, Glithero RJ, Grafham DV, Grant M, Gribble S, Griffiths C, Griffiths M, Hall R, Halls KS, Hammond S, Harley JL, Hart EA, Heath PD, Heathcott R, Holmes SJ, Howden PJ, Howe KL, Howell GR, Huckle E, Humphray SJ, Humphries MD, Hunt AR, Johnson CM, Joy AA, Kay M, Keenan SJ, Kimberley AM, King A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd CR, Lloyd DM, Loveland JE, Lovell J, Martin S, Mashreghi-Mohammadi M, Maslen GL, Matthews L, McCann OT, McLaren SJ, McLay K, McMurray A, Moore MJ, Mullikin JC, Niblett D, Nickerson T, Novik KL, Oliver K, Overton-Larty EK, Parker A, Patel R, Pearce AV, Peck AI, Phillimore B, Phillips S, Plumb RW, Porter KM, Ramsey Y, Ranby SA, Rice CM, Ross MT, Searle SM, Sehra HK, Sheridan E, Skuce CD, Smith S, Smith M, Spraggon L, Squares SL, Steward CA, Sycamore N, Tamlyn-Hall G, Tester J, Theaker AJ, Thomas DW, Thorpe A, Tracey A, Tromans A, Tubby B, Wall M, Wallis JM, West AP, White SS, Whitehead SL, Whittaker H, Wild A, Willey DJ, Wilmer TE, Wood JM, Wray PW, Wyatt JC, Young L, Younger RM, Bentley DR, Coulson A, Durbin R, Hubbard T, Sulston JE, Dunham I, Rogers J, Beck S: The DNA sequence and analysis of human chromosome 6. Nature. 2003 Oct 23;425(6960):805-11. 14574404
  11. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  12. Uhl GR, Sora I, Wang Z: The mu opiate receptor as a candidate gene for pain: polymorphisms, variations in expression, nociception, and opiate responses. Proc Natl Acad Sci U S A. 1999 Jul 6;96(14):7752-5. 10393893
  13. Chuang TK, Killam KF Jr, Chuang LF, Kung HF, Sheng WS, Chao CC, Yu L, Chuang RY: Mu opioid receptor gene expression in immune cells. Biochem Biophys Res Commun. 1995 Nov 22;216(3):922-30. 7488213
  14. Koch T, Brandenburg LO, Schulz S, Liang Y, Klein J, Hollt V: ADP-ribosylation factor-dependent phospholipase D2 activation is required for agonist-induced mu-opioid receptor endocytosis. J Biol Chem. 2003 Mar 14;278(11):9979-85. Epub 2003 Jan 7. 12519790
  15. Zhang P, Johnson PS, Zollner C, Wang W, Wang Z, Montes AE, Seidleck BK, Blaschak CJ, Surratt CK: Mutation of human mu opioid receptor extracellular "disulfide cysteine" residues alters ligand binding but does not prevent receptor targeting to the cell plasma membrane. Brain Res Mol Brain Res. 1999 Oct 1;72(2):195-204. 10529478
  16. Wang D, Sadee W, Quillan JM: Calmodulin binding to G protein-coupling domain of opioid receptors. J Biol Chem. 1999 Jul 30;274(31):22081-8. 10419536
  17. Law PY, Wong YH, Loh HH: Molecular mechanisms and regulation of opioid receptor signaling. Annu Rev Pharmacol Toxicol. 2000;40:389-430. 10836142
  18. Wang D, Surratt CK, Sadee W: Calmodulin regulation of basal and agonist-stimulated G protein coupling by the mu-opioid receptor (OP(3)) in morphine-pretreated cell. J Neurochem. 2000 Aug;75(2):763-71. 10899953
  19. Suzuki S, Chuang LF, Yau P, Doi RH, Chuang RY: Interactions of opioid and chemokine receptors: oligomerization of mu, kappa, and delta with CCR5 on immune cells. Exp Cell Res. 2002 Nov 1;280(2):192-200. 12413885
  20. Massotte D, Brillet K, Kieffer B, Milligan G: Agonists activate Gi1 alpha or Gi2 alpha fused to the human mu opioid receptor differently. J Neurochem. 2002 Jun;81(6):1372-82. 12068084
  21. Feng GJ, Kellett E, Scorer CA, Wilde J, White JH, Milligan G: Selective interactions between helix VIII of the human mu-opioid receptors and the C terminus of periplakin disrupt G protein activation. J Biol Chem. 2003 Aug 29;278(35):33400-7. Epub 2003 Jun 16. 12810704
  22. Onoprishvili I, Andria ML, Kramer HK, Ancevska-Taneva N, Hiller JM, Simon EJ: Interaction between the mu opioid receptor and filamin A is involved in receptor regulation and trafficking. Mol Pharmacol. 2003 Nov;64(5):1092-100. 14573758
  23. Wang D, Sun X, Bohn LM, Sadee W: Opioid receptor homo- and heterodimerization in living cells by quantitative bioluminescence resonance energy transfer. Mol Pharmacol. 2005 Jun;67(6):2173-84. Epub 2005 Mar 18. 15778451
  24. Pascal G, Milligan G: Functional complementation and the analysis of opioid receptor homodimerization. Mol Pharmacol. 2005 Sep;68(3):905-15. Epub 2005 Jun 20. 15967873
  25. Choi HS, Kim CS, Hwang CK, Song KY, Wang W, Qiu Y, Law PY, Wei LN, Loh HH: The opioid ligand binding of human mu-opioid receptor is modulated by novel splice variants of the receptor. Biochem Biophys Res Commun. 2006 May 19;343(4):1132-40. Epub 2006 Mar 23. 16580639
  26. Ancevska-Taneva N, Onoprishvili I, Andria ML, Hiller JM, Simon EJ: A member of the heat shock protein 40 family, hlj1, binds to the carboxyl tail of the human mu opioid receptor. Brain Res. 2006 Apr 7;1081(1):28-33. Epub 2006 Mar 20. 16542645
  27. Roumy M, Lorenzo C, Mazeres S, Bouchet S, Zajac JM, Mollereau C: Physical association between neuropeptide FF and micro-opioid receptors as a possible molecular basis for anti-opioid activity. J Biol Chem. 2007 Mar 16;282(11):8332-42. Epub 2007 Jan 15. 17224450
  28. Lopez A, Salome L: Membrane functional organisation and dynamic of mu-opioid receptors. Cell Mol Life Sci. 2009 Jul;66(13):2093-108. doi: 10.1007/s00018-009-0008-4. Epub 2009 Mar 20. 19300905
  29. Talbot JN, Skifter DA, Bianchi E, Monaghan DT, Toews ML, Murrin LC: Regulation of mu opioid receptor internalization by the scaffold protein RanBPM. Neurosci Lett. 2009 Dec 11;466(3):154-8. doi: 10.1016/j.neulet.2009.09.048. Epub 2009 Sep 27. 19788913
  30. Jin J, Kittanakom S, Wong V, Reyes BA, Van Bockstaele EJ, Stagljar I, Berrettini W, Levenson R: Interaction of the mu-opioid receptor with GPR177 (Wntless) inhibits Wnt secretion: potential implications for opioid dependence. BMC Neurosci. 2010 Mar 9;11:33. doi: 10.1186/1471-2202-11-33. 20214800
  31. Gris P, Gauthier J, Cheng P, Gibson DG, Gris D, Laur O, Pierson J, Wentworth S, Nackley AG, Maixner W, Diatchenko L: A novel alternatively spliced isoform of the mu-opioid receptor: functional antagonism. Mol Pain. 2010 Jun 2;6:33. doi: 10.1186/1744-8069-6-33. 20525224
  32. Bergen AW, Kokoszka J, Peterson R, Long JC, Virkkunen M, Linnoila M, Goldman D: Mu opioid receptor gene variants: lack of association with alcohol dependence. Mol Psychiatry. 1997 Oct-Nov;2(6):490-4. 9399694
  33. Bond C, LaForge KS, Tian M, Melia D, Zhang S, Borg L, Gong J, Schluger J, Strong JA, Leal SM, Tischfield JA, Kreek MJ, Yu L: Single-nucleotide polymorphism in the human mu opioid receptor gene alters beta-endorphin binding and activity: possible implications for opiate addiction. Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9608-13. 9689128