These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Femtomolar concentrations of dynorphins protect rat mesencephalic dopaminergic neurons against inflammatory damage.
    Author: Liu B, Qin L, Yang SN, Wilson BC, Liu Y, Hong JS.
    Journal: J Pharmacol Exp Ther; 2001 Sep; 298(3):1133-41. PubMed ID: 11504811.
    Abstract:
    The hallmark of Parkinson's disease is the death of nigral dopaminergic neurons, and inflammation in the brain has been increasingly associated with the pathogenesis of this neurological disorder. Dynorphins are among the major opioid peptides in the striato-nigral pathway and are important in regulating dopaminergic neuronal activities. However, it is not clear whether dynorphins play a role in the survival of nigral dopaminergic neurons. We have recently demonstrated that lipopolysaccharide (LPS) activates the brain immune cells microglia, in vitro and in vivo, to release neurotoxic factors to degenerate dopaminergic neurons. The purpose of this study was to explore the neuroprotective effect of dynorphins in the inflammation-mediated degeneration of dopaminergic neurons in rat midbrain neuron-glia cultures. LPS-induced neurotoxicity was significantly reduced by treatment with ultra low concentrations (10(-13)--10(-15) M) of the kappa-opioid receptor agonist dynorphin A (1--17) or the receptor binding ineffective [des-Tyr(1)]dynorphin A (2--17), but not by U50488, a synthetic kappa-receptor agonist. The glia-mediated neuroprotective effect of dynorphins was further supported by the finding that femtomolar concentrations of dynorphins did not prevent the killing of dopaminergic neurons by 6-hydroxydopamine. However, ultra low concentrations of dynorphins inhibited LPS-induced production of superoxide. These results suggest a glia-mediated and conventional opioid receptor-unrelated mechanism of action for the neuroprotective effect of ultra low concentrations of dynorphins. Understanding the underlying mechanisms of action should further define the roles of dynorphins in the regulation of dopaminergic neurons and help devise novel strategies to combat neurodegenerative diseases.
    [Abstract] [Full Text] [Related] [New Search]