title: The presence of endogenous morphine signaling in animals.
abstract: Recent empirical findings have contributed valuable mechanistic information in support of a regulated de novo biosynthetic pathway for chemically authentic morphine and related morphinan alkaloids within animal cells. Importantly, we and others have established that endogenously expressed morphine represents a key regulatory molecule effecting local circuit autocrine/paracrine cellular signaling via a novel mu(3) opiate receptor coupled to constitutive nitric oxide production and release. The present report provides an integrated review of the biochemical, pharmacological, and molecular demonstration of mu(3) opiate receptors in historical linkage to the elucidation of mechanisms of endogenous morphine production by animal cells and organ systems. Ongoing research in this exciting area provides a rare window of opportunity to firmly establish essential biochemical linkages between dopamine, a morphine precursor, and animal biosynthetic pathways involved in morphine biosynthesis that have been conserved throughout evolution.
authors.affiliation: Neuroscience Research Institute, State University of New York-College at Old Westbury, P.O. Box 210, Old Westbury, NY 11568, USA. gstefano@sunynri.org
authors.forename: George B
authors.initials: GB
authors.lastname: Stefano
authors.forename: Patrick
authors.initials: P
authors.lastname: Cadet
authors.forename: Richard M
authors.initials: RM
authors.lastname: Kream
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
mesh_terms: D000818:Animals; D001483:Base Sequence; D006801:Humans; D008969:Molecular Sequence Data; D009020:Morphine / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis; D017450:Receptors, Opioid, mu / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D017450:Receptors, Opioid, mu; D009569:Nitric Oxide; D009020:Morphine
references.citation: Brain Res Mol Brain Res. 1999 Dec 10;74(1-2):242-6
references.pmid: 10640698
references.citation: Brain Res Mol Brain Res. 2002 Feb 28;99(1):26-33
references.pmid: 11869805
references.citation: J Pharmacol Exp Ther. 1987 Aug;242(2):583-7
references.pmid: 3497260
references.citation: J Pharmacol Exp Ther. 1989 Nov;251(2):461-8
references.pmid: 2553920
references.citation: Cell Signal. 1999 Mar;11(3):189-93
references.pmid: 10353693
references.citation: Brain Res Mol Brain Res. 2001 Jan 31;86(1-2):184-8
references.pmid: 11165385
references.citation: Endothelium. 2000;7(3):185-91
references.pmid: 10912912
references.citation: Brain Res Mol Brain Res. 2000 May 5;77(2):267-9
references.pmid: 10837921
references.citation: Eur J Pharmacol. 1991 Aug 16;201(1):121-2
references.pmid: 1665419
references.citation: Neuro Endocrinol Lett. 2005 Apr;26(2):89-97
references.pmid: 15855878
references.citation: J Biol Chem. 2002 Sep 13;277(37):33711-9
references.pmid: 12093814
references.citation: J Neurosci Res. 1997 Nov 1;50(3):450-6
references.pmid: 9364330
references.citation: Nature. 1977 Jun 9;267(5611):495-9
references.pmid: 195217
references.citation: Med Sci Monit. 2004 Jun;10(6):MS1-5
references.pmid: 15173678
references.citation: Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8495-500
references.pmid: 15937106
references.citation: Adv Neuroimmunol. 1994;4(2):57-67
references.pmid: 7952829
references.citation: Expert Opin Biol Ther. 2005 Jul;5(7):893-906
references.pmid: 16018736
references.citation: Med Sci Monit. 2004 Dec;10(12):BR433-9
references.pmid: 15567973
references.citation: Eur J Pharmacol. 1994 Apr 1;255(1-3):33-7
references.pmid: 8026553
references.citation: Med Sci Monit. 2005 May;11(5):MS1-5
references.pmid: 15874894
references.citation: Life Sci. 1993;53(1):PL1-5
references.pmid: 7685846
references.citation: J Immunol. 2005 Dec 1;175(11):7357-62
references.pmid: 16301642
references.citation: Med Sci Monit. 2004 Oct;10(10):BR351-5
references.pmid: 15448587
references.citation: Brain Res. 1994 Dec 26;667(2):229-37
references.pmid: 7697360
references.citation: Peptides. 1990 Mar-Apr;11(2):311-31
references.pmid: 2162533
references.citation: Biochem Biophys Res Commun. 1998 Aug 28;249(3):838-43
references.pmid: 9731223
references.citation: Med Sci Monit. 2006 Oct;12(10):RA207-19
references.pmid: 17006413
references.citation: J Cardiovasc Pharmacol. 1998 Jun;31(6):862-8
references.pmid: 9641470
references.citation: Life Sci. 1987 Jan 19;40(3):301-6
references.pmid: 3796227
references.citation: Brain Res Mol Brain Res. 2004 Oct 22;129(1-2):117-23
references.pmid: 15469888
references.citation: Trends Neurosci. 2000 Sep;23(9):436-42
references.pmid: 10941194
references.citation: J Immunol. 2007 Nov 1;179(9):5839-44
references.pmid: 17947657
references.citation: J Immunol. 2003 May 15;170(10):5118-23
references.pmid: 12734358
references.citation: Med Sci Monit. 2007 Aug;13(8):BR163-7
references.pmid: 17660719
references.citation: Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9316-20
references.pmid: 1329092
references.citation: J Biol Chem. 2006 Mar 24;281(12):8082-9
references.pmid: 16434406
references.citation: Immunopharmacology. 1992 Jan-Feb;23(1):57-61
references.pmid: 1314788
references.citation: J Immunol. 1994 Jun 15;152(12):5845-52
references.pmid: 8207211
references.citation: Neuropharmacology. 1994 Feb;33(2):189-92
references.pmid: 7518573
references.citation: Brain Res. 1997 Jul 18;763(1):63-8
references.pmid: 9272829
references.citation: Ann Trop Med Parasitol. 2002 Apr;96(3):309-16
references.pmid: 12061977
references.citation: Med Sci Monit. 2001 Nov-Dec;7(6):1123-8
references.pmid: 11687719
references.citation: J Immunol. 1995 Feb 1;154(3):1323-30
references.pmid: 7822801
references.citation: Trends Pharmacol Sci. 1993 Mar;14(3):84-6
references.pmid: 8387705
references.citation: J Cardiovasc Pharmacol. 1998 Jun;31(6):813-20
references.pmid: 9641464
references.citation: Zhongguo Yao Li Xue Bao. 1998 Sep;19(5):403-7
references.pmid: 10375796
references.citation: Gen Pharmacol. 1997 Jul;29(1):39-47
references.pmid: 9195191
references.citation: Int J Mol Med. 2001 Apr;7(4):419-22
references.pmid: 11254885
references.citation: J Biol Chem. 1995 Dec 22;270(51):30290-3
references.pmid: 8530450
references.citation: Proc Natl Acad Sci U S A. 1986 Dec;83(24):9784-8
references.pmid: 3467337
references.citation: Neuro Endocrinol Lett. 2006 Feb-Apr;27(1-2):21-33
references.pmid: 16648819
references.citation: Proc Natl Acad Sci U S A. 1976 Jun;73(6):2132-6
references.pmid: 1064881
references.citation: Int J Mol Med. 2003 Oct;12(4):485-92
references.pmid: 12964024
references.citation: Life Sci. 1993;52(23):PL255-60
references.pmid: 8502118
references.citation: Med Sci Monit. 2007 Dec;13(12):SC5-6
references.pmid: 18049446
references.citation: Med Sci Monit. 2006 Sep;12(9):HY21-31
references.pmid: 16940938
references.citation: Int J Cardiol. 1998 Apr 30;64 Suppl 1:S61-6
references.pmid: 9687094
references.citation: Neuro Endocrinol Lett. 2002 Aug;23(4):329-34
references.pmid: 12195236
references.citation: Life Sci. 1994;54(11):695-702
references.pmid: 8107518
references.citation: Biochem Pharmacol. 1986 Feb 1;35(3):361-4
references.pmid: 3004499
references.citation: Semin Cancer Biol. 2008 Jun;18(3):190-8
references.pmid: 18191410
references.citation: Proc Natl Acad Sci U S A. 2004 Sep 28;101(39):14091-6
references.pmid: 15383669
references.citation: Med Sci Monit. 2004 Jun;10(6):MS6-17
references.pmid: 15173679
references.citation: Ann Thorac Surg. 1997 Apr;63(4):1063-9
references.pmid: 9124906
references.citation: Proc Natl Acad Sci U S A. 1986 Jun;83(12):4566-7
references.pmid: 3459191
references.citation: J Neurochem. 1998 Jan;70(1):147-52
references.pmid: 9422357
references.citation: J Infect Dis. 1983 Oct;148(4):656-66
references.pmid: 6355311
references.citation: Crit Rev Immunol. 1996;16(2):109-44
references.pmid: 8879941
references.citation: Int J Cardiol. 1997 Dec 19;62(3):191-7
references.pmid: 9476677
references.citation: Biochemistry. 2001 Nov 27;40(47):14215-23
references.pmid: 11714275
references.citation: Med Sci Monit. 2005 May;11(5):MS31-34
references.pmid: 15874897
references.citation: J Neuroimmunol. 1993 Sep;47(2):189-97
references.pmid: 8370770
references.citation: Med Sci Monit. 2005 Nov;11(11):BR397-404
references.pmid: 16258388
references.citation: Brain Res. 1996 May 25;722(1-2):125-31
references.pmid: 8813357
references.citation: Life Sci. 1997;60(3):237-43
references.pmid: 9000648
references.citation: Biochem Biophys Res Commun. 1984 Jul 18;122(1):265-9
references.pmid: 6331446
references.citation: Brain Res. 1995 Jul 24;686(2):239-48
references.pmid: 7583289
references.citation: J Neuroimmunol. 1998 Mar 15;83(1-2):70-6
references.pmid: 9610675
references.citation: Int J Mol Med. 2001 Aug;8(2):165-9
references.pmid: 11445868
references.citation: Science. 1978 Jan 27;199(4327):447-8
references.pmid: 339350
references.citation: Proc Natl Acad Sci U S A. 1988 Feb;85(4):1267-71
references.pmid: 3422490
references.citation: Med Sci Monit. 2008 Jun;14(6):CS45-49
references.pmid: 18509280
references.citation: Proc Natl Acad Sci U S A. 1985 Aug;82(15):5203-7
references.pmid: 3860854
references.citation: Brain Res. 1998 Apr 20;790(1-2):236-44
references.pmid: 9593913
references.citation: Brain Res Mol Brain Res. 2000 Sep 30;81(1-2):177-80
references.pmid: 11000489
references.citation: Proc Natl Acad Sci U S A. 1981 Oct;78(10):6181-5
references.pmid: 6273857
references.citation: Proc Natl Acad Sci U S A. 1985 Mar;82(6):1852-4
references.pmid: 3920656
references.citation: Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. 1996 Mar;113(3):369-73
references.pmid: 8697194
references.citation: J Physiol Pharmacol. 2004 Mar;55(1 Pt 2):279-88
references.pmid: 15082884
references.citation: Neuro Endocrinol Lett. 2002 Feb;23(1):21-6
references.pmid: 11880858
references.citation: Eur J Pharmacol. 1995 Feb 6;273(3):R5-6
references.pmid: 7737324
references.citation: NIDA Res Monogr. 1990;105:96-102
references.pmid: 1652096
references.citation: Brain Res Mol Brain Res. 2001 Mar 31;88(1-2):155-60
references.pmid: 11295241
references.citation: J Pharmacol Exp Ther. 1991 May;257(2):647-50
references.pmid: 2033511
references.citation: J Parasitol. 2004 Feb;90(1):15-22
references.pmid: 15040662
references.citation: Brain Res Mol Brain Res. 2003 Sep 10;117(1):83-90
references.pmid: 14499484
references.citation: J Immunol. 2000 Jul 1;165(1):339-43
references.pmid: 10861070
references.citation: Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11099-103
references.pmid: 8248214
references.citation: Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):9180-4
references.pmid: 8090788
references.citation: Brain Res. 1993 Nov 12;627(2):210-5
references.pmid: 8298964
references.citation: Semin Cancer Biol. 2008 Jun;18(3):199-210
references.pmid: 18203618
references.citation: Med Sci Monit. 2007 Jun;13(6):RA91-102
references.pmid: 17534245
references.citation: Neurosci Lett. 2000 Oct 27;293(2):135-8
references.pmid: 11027852
references.citation: Neuro Endocrinol Lett. 2004 Oct;25(5):323-30
references.pmid: 15580165
references.citation: Adv Neuroimmunol. 1994;4(2):83-92
references.pmid: 7952831