RGD Reference Report - Melatonin receptor agonist 2-iodomelatonin prevents apoptosis of cerebellar granule neurons via K(+) current inhibition. - Rat Genome Database

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Melatonin receptor agonist 2-iodomelatonin prevents apoptosis of cerebellar granule neurons via K(+) current inhibition.

Authors: Jiao, S  Wu, MM  Hu, CL  Zhang, ZH  Mei, YA 
Citation: Jiao S, etal., J Pineal Res. 2004 Mar;36(2):109-16.
RGD ID: 9588668
Pubmed: (View Article at PubMed) PMID:14962062

Activation of K(+) current plays a critical role in the control of programmed cell death. In the present study, whole-cell patch-clamp recording, a caspase-3 activity assay, and flow cytometric analysis were used to examine the effects of the MT2 melatonin receptor agonist 2-iodomelatonin on the delayed-rectifier K(+) current (IK) and the prevention of apoptosis. It was found that apoptosis of cerebellar granular neurons induced by low-K(+) (5 mm) incubation was associated with an increase in IK amplitude and caspase-3 activity. After 6 hr of low-K(+) treatment, IK was increased by 45% (n = 86). Flow cytometry showed that the apoptosis rate increased by 333% compared with the control neurons. In addition, exposure of cultured granule cells to low K(+) also resulted in a significant activation of caspase-3, by 466%. 2-Iodomelatonin (10 microm in injection pipette) inhibited the IK amplitude recorded from control cells and from cells undergoing apoptosis. However, 2-iodomelatonin only modified the IK-channel activation kinetics of cells under both conditions. Furthermore, 2-iodomelatonin reduced the rate of apoptosis and caspase-3 activation, by 66 and 64%, respectively. The melatonin receptor antagonist, 4P-PDOT, abrogated the effect of 2-iodomelatonin on the IK augmentation, caspase-3 activity, and apoptosis. These results suggest that the neuroprotective effects of melatonin are not only because of its function as a powerful antioxidant, but also to its interactions with specific receptors. The effect of 2-iodomelatonin against apoptosis may be mediated by activating a melatonin receptor, which modulates IK channels and reduces K(+) efflux.

Annotation

Gene Ontology Annotations    

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Mtnr1b  (melatonin receptor 1B)


Additional Information