α-Conotoxin RgIA

α-conotoxin RgIA (RgIA) is a 13 amino acid peptidyl toxin cloned from a genomic DNA library of the marine worm-hunting sea snail, Conus regius¹. RgIA belongs to the α4/3 subfamily of conotoxins (i.e., a family of peptides with four amino acids in the first loop and three in the second loop) and is a potent and selective antagonist of the α9α10 nicotinic acetylcholine receptor (nAChR) subtype, which also shows a weak activity towards α7 nAChR^1,2. RgIA was also shown to inhibit high-voltage-activated (HVA) calcium channel currents in rat dorsal root ganglion (DRG) neurons³.

The nAChRs are acetylcholine-gated ion channels. Given the important physiological roles of nAChRs in pain, inflammation, nicotine addiction, Alzheimer's disease, and Parkinson's disease, specific targeting of the relevant nAChR subtypes is an attractive pharmaceutical strategy. α-conotoxins are among the most promising drug development leads for treating these diseases^4,5. RgIA was shown to be an effective analgesic agent in a rat model of nerve injury and also reduced the immune response contributing to peripheral nerve damage^6,7. Furthermore, RgIA was shown to prevent neuropathic pain induced by oxaliplatin treatment⁸.