NMB-1 (Noxious mechanosensation blocker 1) is an analogue of a peptide isolated from a marine conesnail. This 19 amino acid peptide has shown a 30 fold selectivity in inhibiting slowly adapting mechanically activated currents over rapidly adapting ones. It is an interesting tool to distinguish between RA and SA currents. NMB-1 significantly blocks SA currents at 1 µM in sensory neurons contrary to GsMTx4. Some results suggest that NMB-1 could also block mechanosensitive ion channels in cochlear hair cells at 5 µM.Smartox Biotechnology is pleased to be the first company offering this research tool.

Description:

Product code: NMB001.Category: Mechanosensitive channels.

AA sequence: Phe-Asn-Trp-Arg-Cys-Cys-Leu-Ile-Pro-Cys-Arg-Arg-Asn-His-Lys-Lys-Phe-Phe-Cys-NH₂Disulfide bonds: Cys⁵-Cys¹⁹ and Cys⁶-Cys¹⁰Length (aa): 19Formula: C₁₁₁H₁₆₄N₃₆O₂₁S₄Molecular Weight:  2467.03 DaAppearance: White lyophilized solidSolubility: aqueous bufferCAS number: not availableSource: SyntheticPurity rate: > 95 %

Reference:

High-Threshold Mechanosensitive Ion Channels Blocked by a Novel Conopeptide Mediate Pressure-Evoked Pain

Little is known about the molecular basis of somatosensory mechanotransduction in mammals. We screened a library of peptide toxins for effects on mechanically activated currents in cultured dorsal root ganglion neurons. One conopeptide analogue, termed NMB-1 for noxious mechanosensation blocker 1, selectively inhibits (IC50 1 mM) sustained mechanically activated currents in a subset of sensory neurons. Biotinylated NMB-1 retains activity and binds selectively to peripherinpositive nociceptive sensory neurons. The selectivity of NMB-1 was confirmed by the fact that it has no inhibitory effects on voltage-gated sodium and calcium channels, or ligand-gated channels such as acid-sensing ion channels or TRPA1 channels. Conversely, the tarantula toxin, GsMTx-4, which inhibits stretch-activated ion channels, had no effects on mechanically activated currents in sensory neurons. In behavioral assays, NMB-1 inhibits responses only to high intensity, painful mechanical stimulation and has no effects on low intensity mechanical stimulation or thermosensation. Unexpectedly, NMB-1 was found to also be an inhibitor of rapid FM1-43 loading (a measure of mechanotransduction) in cochlear hair cells. These data demonstrate that pharmacologically distinct channels respond to distinct types of mechanical stimuli and suggest that mechanically activated sustained currents underlie noxious mechanosensation. NMB-1 thus provides a novel diagnostic tool for the molecular definition of channels involved in hearing and pressure-evoked pain.Drew LJ., et al. (2007) PLoS ONE

Molecular mechanisms of mechanotransduction in mammalian sensory neurons

The somatosensory system mediates fundamental physiological functions, including the senses of touch, pain and proprioception. This variety of functions is matched by a diverse array of mechanosensory neurons that respond to force in a specific fashion. Mechanotransduction begins at the sensory nerve endings, which rapidly transform mechanical forces into electrical signals. Progress has been made in establishing the functional properties of mechanoreceptors, but it has been remarkably difficult to characterize mechanotranducer channels at the molecular level. However, in the past few years, new functional assays have provided insights into the basic properties and molecular identity of mechanotransducer channels in mammalian sensory neurons. The recent identification of novel families of proteins as mechanosensing molecules will undoubtedly accelerate our understanding of mechanotransduction mechanisms in mammalian somatosensation.Delmas P., et al. (2011) Nature