Inhibition of swine microglial cell phagocytosis of Cryptococcus neoformans by femtomolar concentrations of morphine.
Microglia are important immune effector cells within the brain. The phagocytosis of nonopsonized Cryptococcus neoformans by swine microglia was used as an in vitro model for studies on cellular mechanisms of opiate-mediated immunomodulation in the brain. Morphine inhibited potently (IC50 approximately 10(-16) M) the phagocytosis of C. neoformans by primary cultures of neonatal pig microglia. The mu opioid agonist Tyr-D-Ala-Gly-N-Me-Phe-Gly-ol (DAMGO) also suppressed phagocytosis but with a much lower potency than morphine (IC50 approximately 10(-8) M). The inhibitory effects of morphine and DAMGO were blocked by equimolar concentrations of naloxone and by the selective mu opiate receptor antagonist beta-funaltrexamine. Pertussis toxin but not cholera toxin reversed the inhibitory effects of both morphine and DAMGO. Our data suggest that morphine inhibits phagocytosis of C. neoformans by swine microglia via a mechanism involving mu opiate receptors coupled to a pertussis toxin-sensitive Gi/G(o) protein signaling pathway.
Sowa
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G
Neuroimmunobiology and Host Defense Laboratory, Minneapolis Medical Research Foundation, MN, USA.
Gekker
G
G
Lipovsky
M M
MM
Hu
S
S
Chao
C C
CC
Molitor
T W
TW
Peterson
P K
PK
D000818:Animals; D003455:Cryptococcus neoformans / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology; D017628:Microglia / Q000187:drug effects* / Q000276:immunology; D009020:Morphine / Q000494:pharmacology*; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D010587:Phagocytosis / Q000187:drug effects*; D013552:Swine
D004745:Enkephalins; D009294:Narcotics; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009271:Naltrexone; C024524:beta-funaltrexamine; D009020:Morphine; D019204:GTP-Binding Proteins