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CD38: Novel interaction with morphine analgesic pathways in mice
Author(s) -
Hull Lynn Christine,
Lee Thomas T.,
Chen Li,
Zhang Guo,
Li PinLan,
Dewey William L.,
Smith Forrest L.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a241-a
Subject(s) - morphine , analgesic , cd38 , pharmacology , medicine , biology , microbiology and biotechnology , stem cell , cd34
CD38 is a 45 kDa monomer enzyme complex consisting of both ADP‐ribosylcyclase as well as cADP hydrolase. C38 has been discovered in both neurons and glia of the brain, however, its role in signal transduction is not fully characterized. Experiments were conducted to determine its role in morphine‐induced analgesia in the periaqueductal gray (PAG) of male Swiss‐Webster mice. PAG was removed 30‐min following acute administration of 8 mg/kg morphine s.c. Gene expression of CD38 was significantly increased in the morphine‐treated mice compared to naive mice. Western Immunoblotting demonstrated an increase in the expression of the more active 110 kDa homodimer form of CD38. In addition, the ADP‐ribosylcyclase conversion of β‐NGD + to cGDPR was significantly increased. All of these effects were completely blocked in mice co‐treated with 1 mg/kg naloxone s.c. Other experiments determined the specific activity of CD38 in morphine‐induced analgesia. Nicotinamide is a negative feedback inhibitor of CD38 ADP‐ribosylcyclase. Nicotinamide injected i.p. dose‐dependently antagonized the antinociceptive effects of 8 mg/kg morphine in the 56 °C tail‐withdrawal test. Furthermore, a 500 mg/kg nicotinamide dose decreased the potency of morphine by 9.7‐fold. These results are supported by data from male CD38 −/− knockout mice, which exhibited a decreased analgesic response to morphine in comparison to male C57BL/6J wild‐type mice. Funded by NIH grants: R01‐DA‐01647, T32‐DA‐07027, K05‐DA‐00480, HL‐57244, HL‐75316.