Response to Comment on “Human White Blood Cells Synthesize Morphine: CYP2D6 Modulation”

SummaryClinical observations stemming from widespread employment of restorative L-3,4-dihydroxyphenylalanine (L-DOPA) therapy for management of dyskinesia in Parkinson’s Disease (PD) patients implicate a regulatory role for endogenous morphine in central nervous system dopamine neurotransmission. Reciprocally, it appears that restorative L-DOPA administration has provided us with a compelling in vivo pharmacological model for targeting peripheral sites involved in endogenous morphine expression in human subjects. The biological activities underlying endogenous morphine expression and its interaction with its major precursor dopamine strongly suggest that endogenous morphine systems are reciprocally dysregulated in PD. These critical issues are examined from historical and current perspectives within our short review.

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Parkinson’s disease, L-DOPA, and endogenous morphine: A revisit

Stefano

Mantione

Králíčková

et al. 2012

Med Sci Monit

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Psychiatric Implications of Endogenous Morphine: Up-To-Date Review

Kream,

Stefano,

Ptáček

2010

Fol. Biol.

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For over 30 years empirical studies have repeatedly demonstrated that the biosynthesis of morphine by diverse animal and human tissues occurs. Recently, the blue mussel’s neural tissues and human white blood cells were used to demonstrate the de novo biosynthesis of morphine for small precursor molecules derived from the aromatic amino acid L-tyrosine. Because catecholamine precursors, i.e., L-3,4-dihydroxyphenylalanine (L-DOPA), were also found to be utilized as morphine precursors, a novel reciprocally interactive mechanism is apparent that links catecholamine and opioid pathways in the activation and inhibition of diverse tissue responses. Additionally, these observations provide new insights into morphinergic signalling that transcend analgesia and addiction. We have also linked the biological effects of nitric oxide into a common effect in endogenous morphine signalling. Given the singular importance of dopamine and morphine’s interaction in the CNS, the presence and association of this signalling with nitric oxide all promises to provide novel answers for mental health phenomena, which have been lacking because of the inability in accepting the empirical endogenous morphine studies.

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Opioid peptides and opiate alkaloids in immunoregulatory processes

Stefano¹,

Kream²

2010

aoms

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Among the various non-neuronal cell types known to express and utilize neuropeptides, those of the immune system have received much attention in recent years. In particular, comparative studies in vertebrates and invertebrates have shown that endogenous opioid peptides are engaged in receptor mediated autoregulatory immune and neuroendocrine processes. The majority of these immune processes are stimulatory, as determined by their effects on conformational changes indicative of immunocyte activation, cellular motility, and phagocytosis. Endogenous opioid peptides form an effective network of messenger molecules in cooperation with cytokines, opiate alkaloids, and certain regulatory enzymes (neutral endopeptidase 24.11). Peptide-mediated immunostimulatory effects observed in this system are operationally counteracted by the inhibitory effects of morphine and related opiates. Opioid/opiate signaling processes are mediated by several types of receptors with different degrees of selectivity. Among them the recently identified, opioid insensitive µ3 receptor deserves attention on account of its specificity for opiate alkaloids.

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Response to Comment on “Human White Blood Cells Synthesize Morphine: CYP2D6 Modulation”

Cited by 3 publications

References 9 publications

Parkinson’s disease, L-DOPA, and endogenous morphine: A revisit

Parkinson’s disease, L-DOPA, and endogenous morphine: A revisit

Psychiatric Implications of Endogenous Morphine: Up-To-Date Review

Opioid peptides and opiate alkaloids in immunoregulatory processes

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