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Biological Chemistry

Neuropeptide Signaling Seen In A Different Light

Photoactivated neuropeptides enable researchers to study kinetics of receptor signaling in the brain

by Lauren K. Wolf
February 6, 2012 | A version of this story appeared in Volume 90, Issue 6

Researchers at Harvard Medical School have designed a light-activated neuropeptide for studying signaling between neurons in the brain (Neuron, DOI: 10.1016/j.neuron.2011.11.016). Like small-molecule neurotransmitters, the larger neuropeptides trigger protein receptors and alter neuron firing. But the peptides diffuse more slowly and travel over larger regions than neurotransmitters, making them difficult to study. Matthew R. Banghart and Bernardo L. Sabatini have now developed a photoactivatable version of the neuropeptide [Leu5]-enkephalin, an opioid. By virtue of a carboxynitrobenzyl protecting group (shown in red) that can be cleaved from the peptide with ultraviolet light, the scientists are able to precisely control where, when, and how much of the active peptide gets released in brain tissue. After equilibrating the protected neuropeptide in rat brain slices, they activated the enkephalin with a laser beam and, for the first time, measured how fast it triggered opioid receptors in nearby neurons. In doing so, Banghart and Sabatini also determined that the neuropeptide can travel as far as 300 µm from its release point and still activate nerve receptors. This is remarkable, Banghart says, given that small-molecule neurotransmitters travel only a few micrometers after being released from nerve cells in synapses.


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