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


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.
Zhu
Wei
W
Neuroscience Research Institute, State University of New York College at Old Westbury, 11568, USA.
Mantione
Kirk J
KJ
Shen
Lihua
L
Stefano
George B
GB
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D044182:Benzylisoquinolines / Q000494:pharmacology*; D049872:Bivalvia / Q000187:drug effects* / Q000378:metabolism*; D005724:Ganglia / Q000187:drug effects* / Q000378:metabolism*; D066298:In Vitro Techniques; D007980:Levodopa / Q000493:pharmacokinetics / Q000494:pharmacology*; D009020:Morphine / Q000378:metabolism*
D000470:Alkaloids; D044182:Benzylisoquinolines; D007980:Levodopa; D009020:Morphine; C003298:reticuline