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05 May 2005 : Original article  

In vivo and in vitro L-DOPA and reticuline exposure increases ganglionic morphine levels.

Wei Zhu, Kirk J. Mantione, Lihua Shen, George B. Stefano

Med Sci Monit 2005; 11(5): MS1-5 :: ID: 16151

Abstract

BACKGROUND: Given the presence of morphine, its metabolites and precursors, i.e., reticuline, in mammalian and invertebrate tissues, it has become imperative to determine if exposing tissues to putative opiate alkaloid and dopamine precursors would result in increasing endogenous morphine levels. MATERIAL/METHODS: Endogenous morphine levels were determined by high performance liquid chromatography coupled to electrochemical detection and radioimmunoassay, following incubation of Mytilus edulis pedal ganglia with reticuline or L-DOPA. Injection of L-DOPA or reticuline into healthy animals was via the foot. RESULTS: Ganglia incubated in vitro with reticuline or L-DOPA for 1 hour exhibited a concentration and time dependent statistically significant increase in their endogenous morphine levels (5.0 +/- 0.47, 3.6 +/- 0.45 ng/ganglion, respectively). Injection of intact, healthy animals with reticuline or L-DOPA also results in significantly higher endogenous ganglionic morphine levels. CONCLUSIONS: Taken together, we show that L-DOPA is being converted to morphine, demonstrating that pedal ganglia can synthesize morphine from these putative precursors in vitro and in vivo. This is the first demonstration of morphine being synthesized in a normal, healthy free living animal.

Keywords: Benzylisoquinolines - pharmacology, Bivalvia - drug effects, Bivalvia - metabolism, Ganglia - drug effects, Ganglia - metabolism, Levodopa - pharmacokinetics, Alkaloids - pharmacology, Benzylisoquinolines - pharmacology, Bivalvia - metabolism, Ganglia - metabolism, Levodopa - pharmacology, Morphine - metabolism

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