Morphine 6 glucuronide stimulates nitric oxide release in mussel neural tissues: evidence for a morphine 6 glucuronide opiate receptor subtype |
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Authors: | K Mantione W Zhu C Rialas F Casares P Cadet A L Franklin J Tonnesen G B Stefano |
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Institution: | (1) Neuroscience Research Institute, State University of New York at Old Westbury, P.O. Box 210, Old Westbury, New York 11568 (USA), Fax: +1 516 876 2727; e-mail: gstefano@optonline.net, US |
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Abstract: | We have previously demonstrated that Mytilus edulis pedal ganglia contain opiate alkaloids, i.e., morphine and morphine 6 glucuronide (M6G), as well as mu opiate receptor subtype
fragments exhibiting high sequence similarity to those found in mammals. Now we demonstrate that M6G stimulates pedal ganglia
constitutive nitric oxide (NO) synthase (cNOS)-derived NO release at identical concentrations and to similar peak levels as
morphine. However, the classic opiate antagonist, naloxone, only blocked the ability of morphine to stimulate cNOS-derived
NO release and not that of M6G. CTOP, a mu-specific antagonist, blocked the ability of M6G to induce cNOS-derived NO release
as well as that of morphine, suggesting that a novel mu opiate receptor was present and selective toward M6G. In examining
a receptor displacement analysis, both opiate alkaloids displaced 3H]-dihydromorphine binding to the mu opiate receptor subtype. However, morphine exhibited a twofold higher affinity, again
suggesting that a novel mu opiate receptor may be present.
Received 1 November 2001; received after revision 1 February 2002; accepted 1 February 2002 |
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Keywords: | , Nitric oxide, morphine 6 glucuronide, morphine, mu receptor, CTOP, nervous tissue, invertebrate, mussel, |
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