α-Conotoxin PIA – Ion Channels and Transporters

α-conotoxin PIA has been isolated from the venom of the marine snail Conus purpurascens. α-conotoxin PIA preferentially targets neuronal AChR subtypes containing α6 subunits. The peptide displays 75-fold higher affinity for rat α6/α3β2β3 nAChRs over rat α3β2 nAChRs. α-conotoxin PIA potently inhibits human chimeric α6/α3β2β3 nAChRs (IC50 of 1.7 nM) and provided similar results on rat chimeric α6/α3β2β3 (IC50 of 0.95 nM). 10 μM α-conotoxin PIA has no effect on the adult form of the human muscle nAChR demonstrating a high specificity for α6-containing neuronal nAChRs. The peptide has no effect on α2- and α4-containing neuronal nAChRs. α6-containing neuronal nAChRs are highly expressed in several catecholaminergic nuclei (locus coeruleus, ventral tegmental area and substantia nigra), play a significant role in nicotinic reward and dependence, and is a therapeutic target of interest in Parkinson disease.

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