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Homology‐guided mutational analysis reveals the functional requirements for antinociceptive specificity of collapsin response mediator protein 2‐derived peptides
Author(s) -
Moutal Aubin,
Li Wennan,
Wang Yue,
Ju Weina,
Luo Shizhen,
Cai Song,
FrançoisMoutal Liberty,
PerezMiller Samantha,
Hu Jackie,
Dustrude Erik T,
Vanderah Todd W,
Gokhale Vijay,
Khanna May,
Khanna Rajesh
Publication year - 2018
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.13737
Subject(s) - dorsal root ganglion , nociception , neuropathic pain , voltage dependent calcium channel , neuroscience , t type calcium channel , pharmacology , calcium channel , depolarization , calcium , chemistry , medicine , biology , sensory system , receptor
N-type voltage-gated calcium (Ca v 2.2) channels are critical determinants of increased neuronal excitability and neurotransmission accompanying persistent neuropathic pain. Although Ca v 2.2 channel antagonists are recommended as first-line treatment for neuropathic pain, calcium-current blocking gabapentinoids inadequately alleviate chronic pain symptoms and often exhibit numerous side effects. Collapsin response mediator protein 2 (CRMP2) targets Ca v 2.2 channels to the sensory neuron membrane and allosterically modulates their function. A 15-amino-acid peptide (CBD3), derived from CRMP2, disrupts the functional protein-protein interaction between CRMP2 and Ca v 2.2 channels to inhibit calcium influx, transmitter release and acute, inflammatory and neuropathic pain. Here, we have mapped the minimal domain of CBD3 necessary for its antinociceptive potential.