Neuronal calcium channel inhibitors. Synthesis of omega-conotoxin GVIA and effects on 45Ca uptake by synaptosomes.
We previously described a 27-amino acid peptide neurotoxin from the venom of Conus geographus, omega-conotoxin GVIA, which inhibits neuronal voltage-activated calcium channels. In this paper we describe the total synthesis of omega-conotoxin GVIA and demonstrate that it efficiently blocks voltage-activated uptake of 45Ca by standard synaptosomal preparations from chick brain. Dihydropyridines do not block 45Ca uptake under these conditions. Thus, the omega-conotoxin-sensitive, but dihydropyridine-insensitive uptake of 45Ca2+ by chick brain synaptosomes serves as a functional assay for a Ca channel target of omega-conotoxin. The use of synthetic GVIA should rapidly accelerate our understanding of the molecular biology of Ca2+ channels and their role in neuronal function.
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers; D002132:Calcium Radioisotopes; D002645:Chickens; D002851:Chromatography, High Pressure Liquid; D004095:Dihydropyridines; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008978:Mollusk Venoms / Q000138:chemical synthesis* / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism*; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D002132:Calcium Radioisotopes; D004095:Dihydropyridines; D007473:Ion Channels; D008978:Mollusk Venoms; D011725:Pyridines; C038806:1,4-dihydropyridine; D020866:omega-Conotoxin GVIA; D012964:Sodium; D002118:Calcium