Dynorphin blocks opioid inhibition of macrophage-colony stimulating factor-induced proliferation of bone marrow cells.
We previously reported that morphine inhibits macrophage-colony stimulating factor (M-CSF)-induced proliferation of mouse bone marrow cells, both in vivo and in vitro, in a dose-dependent manner. We now report that either dynorphin A-(1-13) or dynorphin A-(1-10) amide, though having no effect on proliferation by themselves at concentrations less than 0.1 mM, can block the inhibitory effect of morphine both in vivo and in vitro, in a dose-dependent manner. The opioid antagonist naloxone can also block morphine's inhibitory effect on bone marrow cell proliferation in vivo, but has no effect in vitro. Dynorphin A-(1-13) was also able to block the dramatic reduction of spleen weight observed in animals chronically treated with morphine. Thus dynorphin, which has previously been shown to antagonize morphine analgesia, is also able to antagonize some of the immunosuppressive effects of morphine.
Department of Pharmacology, University of Minnesota Medical School, Minneapolis 55455.
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D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D003114:Colony-Forming Units Assay; D004399:Dynorphins / Q000494:pharmacology*; D016173:Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051379:Mice; D009020:Morphine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*; D013154:Spleen / Q000187:drug effects
D000700:Analgesics; D010446:Peptide Fragments; D009270:Naloxone; C026843:dynorphin (1-13); D004399:Dynorphins; D009020:Morphine; C039666:dynorphin amide (1-10); D016173:Macrophage Colony-Stimulating Factor