Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mu3 opiate receptor subtype has been characterized by various binding assays as opiate alkaloid selective (e.g. morphine) and opioid peptide (e.g. methionine enkephalin) insensitive. This opiate receptor subtype has been found on human, including cancer cell lines, and invertebrate tissues, demonstrating that it has been conserved during evolution. Furthermore, in numerous reports, this receptor is coupled to constitutive nitric oxide release. In this regard, for example, morphine immune down regulating activities parallels those actions formerly attributed to nitric oxide. We have now identified the mu3 receptor at the molecular level and sequence analysis of the isolated cDNA suggests that it is a novel, alternatively spliced variant of the mu opiate receptor gene (MOR). Furthermore, using Northern blot, reverse transcription coupled to polymerase chain reaction (RT-PCR) and sequence analysis, we have demonstrated the expression of this new mu variant in human vascular tissue, mononuclear cells, polymorphonuclear cells, and human neuroblastoma cells. The presence of this mu splice variant, adds to the growing body of evidence supporting the hypothesis that morphine is an endogenous signaling molecule in neural, immune and vascular systems. In addition to their use in the treatment of pain, opioid peptides appear to be important in the growth regulation of normal and neoplastic tissue. This review will focus on the influence of opiate alkaloids, e.g., morphine, on tumor growth, with emphasis on immuno-regulatory and antiproliferative mechanisms.
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PMID:Endogenous morphinergic signaling and tumor growth. 1535 48

We surmise that opioid peptides, i.e., methionine enkephalin, first arose during evolution as modulators of cellular immune function given their immune actions and the presence of enkelytin, a potent antibacterial peptide, and its precursor proenkephalin in animals 500 million years divergent in evolution. Pain probably emerged from this perspective because of its association with proinflammatory events. Endogenous morphine appears to exert positive effects on homeostasis by limiting the degree of excitation. Supporting this view is the fact that the mu3 opiate receptor subtype, which is opioid peptide insensitive and morphine selective, is coupled to constitutive nitric oxide release, which also has this down regulating action in neural, immune, vascular and gastrointestinal tissues. Thus, morphine down regulates immune processes in addiction, an action/function that it appears to normally perform when the situation calls for this action and by so doing in this natural setting, sustains life.
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PMID:Pain, immunity, opiate and opioid compounds and health. 1587

Nitric oxide (NO) signalling is at the forefront of intense research interest because its many effects remain controversial and seemingly contradictory. This paper examines its role as a potential mediator of pain and tolerance. Within this context discussion covers endogenous morphine, documenting its ability to be made in animal tissues, including nervous tissue, and in diverse animal phyla. Supporting morphine as an endogenous signalling molecule is the presence of the newly cloned mu3 opiate receptor subtype found in animal (including human) immune, vascular and neural tissues, which is coupled to NO release. Importantly, this mu opiate receptor subtype is morphine-selective and opioid peptide-insensitive, further highlighting the presence of morphinergic signalling coupled to NO release. These findings provide novel insights into pain and tolerance as morphinergic signalling exhibits many similarities with NO actions. Taken together, a select morphinergic signalling system utilising NO opens the gate for the development of novel pharmaceuticals and/or the use of old pharmaceuticals in new ways.
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PMID:Endogenous morphine: opening new doors for the treatment of pain and addiction. 1601 36