Ly. Kong et al., Reduction of lipopolysaccharide-induced neurotoxicity in mouse mixed cortical neuron/glia cultures by ultralow concentrations of dynorphins, J BIOMED SC, 7(3), 2000, pp. 241-247
Previously we reported that ultralow concentrations of dynorphins (10(-16)
to 10(-12) M) inhibited lipopolysaccharide (LPS)-induced production of nitr
ic oxide (NO) and proinflammatory cytokines in mouse glia without the parti
cipation of kappa-opioid receptors. In the current study using mouse cortic
al neuron-glia cocultures, we examined the possibility that inhibition of g
lia inflammatory response by dynorphins might be neuroprotective for neuron
s. LPS, in a concentration-dependent manner, markedly increased the release
of lactate dehydrogenase (LDH), an indicator of cellular injury, Ultralow
concentrations (10(-14) to 10(-12) M) of dynorphin (dyn) A-(1-8) significan
tly prevented the LPS-induced release of LDH, loss of neurons, and changes
in cell morphology, in addition to inhibition of LPS-induced nitrite produc
tion. Meanwhile, ultralow concentrations (10(-15) to 10(-13) M) Of des-[Tyr
(1)]-dyn A-(2-17), a nonopioid peptide which does not bind to kappa-opiod r
eceptors exhibited the same inhibitory effect as dyn A-(1-17). These result
s suggest that dynorphins at ultralow concentrations are capable of reducin
g LPS-induced neuronal injury and these neuroprotective effects of dynorphi
ns are not mediated by classical opioid receptors, Copyright (C) 2000 Natio
nal Science Council, ROC and S. Karger AG. Basel.