The Effect of L-Dopa on Endongenous Morphine Production 
and the Mu3 Opiate Receptor
 
Dhruv Vasishtha, RHS ‘07 
(with Kamalakar Atluri, Herricks ‘06)

Morphine, an alkaloid from the Papaver somniferum (opium poppy plant), is a powerful analgesic and the drug of choice for the rapid pain relief of patients, though it is highly addictive. Numerous studies have shown low levels of morphine in animal and human tissues; until recently, these minute amounts of morphine were thought to be of dietary origin (exogenous). However, irrefutable evidence of endogenous morphine, morphine that is produced naturally within the cell, was presented in a mass spectrometry experiment using isotopic oxygen that was shown to be incorporated in the morphine molecule. Endogenous morphine is produced via a biosynthetic pathway that features chemical precursors like reticuline, norlaudanosoline, and levodopa (L-Dopa). This novel project shows that SH-SY5Y (neuroblastoma) cells treated with known amounts of L-Dopa produced morphine endogenously, as quantitatively measured by Radioimmunoassay (RIA), after solid-phase extraction. Furthermore, the gene expression of the Mm3 Opiate Receptor (MOR) was upregulated in SH-SY5Y cells treated with L-Dopa, as evaluated by RT-PCR. Taken together, these studies demonstrate that a morphine precursor like L-Dopa leads to the biosynthesis and production of morphine in animal tissue. Moreover, these results suggest the exciting possibility that a morphine precursor may be administered for palliative care, in place of morphine.