title: Dopamine is necessary to endogenous morphine formation in mammalian brain in vivo.
abstract: Morphine, the most used compound among narcotic analgesics, has been shown to be endogenously present in different mammalian/invertebrate normal tissues. In this study, we used mice that cannot make dopamine due to a genetic deletion of tyrosine hydroxylase specifically in dopaminergic neurons, to test the hypothesis that endogenous dopamine is necessary to endogenous morphine formation in vivo in mammalian brain. When dopamine was lacking in brain neurons, endogenous morphine was missing in brain mouse whereas it could be detected in brain from wild type rodent at a picogram range. Our data prove for the first time that endogenous dopamine is necessary to endogenous morphine formation in normal mammalian brain. Morphine synthesis appears to be originated from dopamine through L-tyrosine in normal brain tissue. Morphine synthesis is not considered to occur inside the same neuron in normal tissue; released dopamine might be transported into morphinergic neuron and further transformed into morphine. A physiological role for endogenous morphine is suggested considering that dopamine could modulate thermal threshold through endogenous morphine formation in vivo. Thus, dopamine and endogenous opiates/opioid peptides may be interconnected in the physiological processes; yet, endogenous morphine may represent a basic link of this chain.
authors.affiliation: Institute of Medicine and Public Health, University of Verona, Verona, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Neri
authors.forename: Carla
authors.initials: C
authors.lastname: Ghelardini
authors.forename: Bethany
authors.initials: B
authors.lastname: Sotak
authors.forename: Richard D
authors.initials: RD
authors.lastname: Palmiter
authors.forename: Massimo
authors.initials: M
authors.lastname: Guarna
authors.forename: George
authors.initials: G
authors.lastname: Stefano
authors.forename: Enrica
authors.initials: E
authors.lastname: Bianchi
mesh_terms: D000818:Animals; D001833:Body Temperature Regulation / Q000502:physiology; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D004298:Dopamine / Q000096:biosynthesis / Q000172:deficiency*; D051379:Mice; D018345:Mice, Knockout; D009020:Morphine / Q000378:metabolism*; D018847:Opioid Peptides / Q000096:biosynthesis*; D012684:Sensory Thresholds / Q000502:physiology; D013697:Thermosensing / Q000502:physiology; D014443:Tyrosine / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics
chemical_list: D018847:Opioid Peptides; D014443:Tyrosine; D009020:Morphine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine