Brain research bulletin
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Brain research bulletin · Mar 2010
Comparative StudyComparative biochemical and pharmacological characterization of a novel, NOP receptor selective hexapeptide, Ac-RYYRIR-ol.
Nociceptin/orphanin FQ (N/OFQ) is an endogenous neuropeptide, which is widely distributed in central and peripheral nervous system. Some N/OFQ sequence unrelated hexapeptides can effectively bind to the N/OFQ peptide (NOP) receptor and they were used as template for structure-activity studies that lead to discovery of the new NOP selective ligands. In the present study, the pharmacological profile of the novel hexapeptide Ac-RYYRIR-ol was investigated using various in vitro assays including receptor binding and G-protein activation in rat brain membranes, mouse and rat vas deferens, guinea pig ileum, mouse colon and Ca(2+) mobilization assay in chinese hamster ovary (CHO) cells co-expressing the human recombinant NOP receptor and the C-terminally modified Galpha(qi5) protein. ⋯ In the mouse colon Ac-RYYRIR-ol produced concentration dependent contractile effects with similar potency and maximal effects as N/OFQ. Finally, in the Ca(2+) mobilization assay performed with CHO-hNOP-Galpha(qi5) cells Ac-RYYRIR-ol displayed lower potency and maximal effects (alpha=0.87) compared with N/OFQ. In conclusion, the novel NOP receptor selective hexapeptide Ac-RYYRIR-ol has been shown to have fine selectivity, high potency, furthermore agonist and antagonist effects toward the NOP receptors were measured in various assays; this is likely due to its partial agonist pharmacological activity.
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Brain research bulletin · Mar 2010
LetterResveratrol is neuroprotective because it is not a direct activator of Sirt1-A hypothesis.
The plant polyphenol resveratrol (3,5,4'-trihydroxystilbene) has been touted to have multiple health benefits. A commonly cited mechanism of resveratrol action is via the activation of the longevity factor Sir2/Sirt1, whose deacetylase activity on several transcription factors has stress resistance and pro-survival effects. Resveratrol has been shown to be beneficial in various in vitro and in vivo models of central nervous system (CNS) neuron death and degeneration, presumably acting through Sirt1. ⋯ Furthermore, resveratrol may indirectly increase Sirt1 activity in recovering or spared cells via AMPK's elevation of NAD levels, which then translates into an overall beneficial outcome. The hypothesis could potentially be tested via selective AMPK silencing in various neuronal death and degeneration models, to see if the neuroprotective effect of resveratrol will be blunted. If proven true, the hypothesis has important ramifications in how reseveratrol, as well as novel Sirt1 activators, may be best used in treatment of CNS injuries and disorders.