Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

01 November 2005

Tyrosine and tyramine increase endogenous ganglionic morphine and dopamine levels in vitro and in vivo: cyp2d6 and tyrosine hydroxylase modulation demonstrates a dopamine coupling.

Wei Zhu, Kirk J. Mantione, Lihua Shen, Patrick Cadet, Tobias Esch, Yannick Goumon, Enrica Bianchi, Dario Sonetti, George B. Stefano

Med Sci Monit 2005; 11(11): BR397-404 :: ID: 430278

Abstract

BACKGROUND: The ability of animals to make morphine has been in question for the last 30 years. Studies have demonstrated that animals do contain morphine precursors and metabolites, as well as the ability to use some morphine precursors to make morphine. MATERIAL/METHODS: The present study uses excised ganglia from the marine invertebrate Mytilus edulis as well as whole animals. Morphine and dopamine levels were determined by high performance liquid chromatography coupled to electrochemical detection and radioimmunoassay. Tissues and whole animals were also exposed to morphine precursors and exposed to the CYP2D6 inhibitor quinidine and the tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (AMPT). Additionally, via RT-PCR, a cDNA fragment of the CYP2D6 enzyme in the ganglia of M. edulis was identified. RESULTS: Pedal ganglia incubated with either tyramine or tyrosine, or whole animals receiving injections, exhibited a statistically significant concentration- and time-dependent increase in their endogenous morphine and dopamine levels (2.51 +/- 0.76 ng/g for tyrosine and 2.39 +/- 0.64 ng/g for tyramine compared to approximately 1.0 ng/g morphine wet weight). Incubation with quinidine and/or AMPT diminished ganglionic morphine and dopamine synthesis at various steps in the synthesis process. We also demonstrated that CYP2D6 mediates the tyramine to dopamine step in this process, as did tyrosine hydroxylase in the step from tyrosine to L-DOPA. Furthermore, via RT-PCR, we identified a cDNA fragment of the CYP2D6 enzyme in the ganglia, which exhibits 94% sequence identity with its human counterpart. Evidence that tyrosine and tyramine were, in part, being converted to dopamine then morphine, and that this process can be inhibited by altering either or both CYP2D6 or tyrosine hydroxylase, is also provided. CONCLUSIONS: It appears that animals have the ability to make morphine. This process also appears to be dynamic in that the inhibition of one pathway allows the other to continue with morphine synthesis. Moreover, dopamine and morphine synthesis were coupled.

Keywords: Morphine - metabolism, alpha-Methyltyrosine - pharmacology, Tyrosine 3-Monooxygenase - antagonists & inhibitors, Tyrosine - pharmacology, Tyramine - pharmacology, RNA, Messenger - analysis, Quinidine - pharmacology, Mytilus edulis - anatomy & histology, DNA, Complementary - genetics, Molecular Sequence Data, Ganglia, Invertebrate - metabolism, Enzyme Inhibitors - pharmacology, Dopamine - metabolism, Base Sequence, Cytochrome P-450 CYP2D6 - genetics

0 Comments

Editorial

12 September 2022 : Editorial  

Editorial: Treatment with Dual Incretin Receptor Agonists to Maintain Normal Glucose Levels May Also Maintain Normal Weight and Control Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD)

Ana Luisa Ordóñez-Vázquez, Sofía Murúa Beltrán-Gall, Shreya C. Pal, Nahum Méndez-Sánchez
Liver Research Unit, Medica Sur Clinic Foundation, Mexico City, Mexico

DOI: 10.12659/MSM.938365

Med Sci Monit 2022; 28:e938365

SARS-CoV-2/COVID-19

16 September 2022 : Review article  

Effects of Physiotherapy on Rehabilitation and Quality of Life in Patients Hospitalized for COVID-19: A Rev...

Med Sci Monit In Press; DOI: 10.12659/MSM.938141  

12 September 2022 : Clinical Research  

Effect of Vitamin D Concentration on Course of COVID-19

Med Sci Monit In Press; DOI: 10.12659/MSM.937741  

In Press

29 Sep 2022 : Animal Research  

Effect of Antilogous Platelet-Rich Plasma on the Revascularization of Rabbit Prefabricated Flap

Med Sci Monit In Press; DOI: 10.12659/MSM.937718  

26 Sep 2022 : Clinical Research  

Distribution and Determinants of Plasma Homocysteine Levels in a Preconception Population: A Retrospective ...

Med Sci Monit In Press; DOI: 10.12659/MSM.937987  

26 Sep 2022 : Clinical Research  

Latency and Interpeak Interval Values of Auditory Brainstem Response in 73 Individuals with Normal Hearing

Med Sci Monit In Press; DOI: 10.12659/MSM.937847  

23 Sep 2022 : Review article  

A Review of the Role of Ultrasound Radiomics and Its Application and Limitations in the Investigation of Th...

Med Sci Monit In Press; DOI: 10.12659/MSM.937738  

Most Viewed Current Articles

30 Dec 2021 : Clinical Research  

Retrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...

DOI :10.12659/MSM.935379

Med Sci Monit 2021; 27:e935379

13 Nov 2021 : Clinical Research  

Acceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...

DOI :10.12659/MSM.932788

Med Sci Monit 2021; 27:e932788

08 Mar 2022 : Review article  

A Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...

DOI :10.12659/MSM.936292

Med Sci Monit 2022; 28:e936292

01 Nov 2020 : Review article  

Long-Term Respiratory and Neurological Sequelae of COVID-19

DOI :10.12659/MSM.928996

Med Sci Monit 2020; 26:e928996

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750