Evidence for distinct sites coupled to high affinity omega-conotoxin receptors in rat brain synaptic plasma membrane vesicles.
The neuronal Ca2+ channel blocker omega-conotoxin (GVIA) binds with very high affinity (Kd of 0.8 pM) to a single class of receptors in purified rat brain synaptic plasma membrane vesicles. Three types of agents have been found to modulate toxin binding. The affinity of omega-conotoxin is decreased by metal ions or organic cations which interact at the pore of voltage-dependent Ca2+ channels. Dynorphin A [1-13] and related peptides stimulate omega-conotoxin binding by increasing toxin affinity through a nonopiate allosteric mechanism. Venom of the spider Plectreurys tristes inhibits omega-conotoxin binding (IC50 of 30 ng protein/ml) by a noncompetitive allosteric mechanism. These results suggest that omega-conotoxin binding sites exist in a complex with distinct receptors for other agents, all of which may be functionally associated with neuronal Ca2+ channels.
Feigenbaum
P
P
Department of Membrane Biochemistry and Biophysics. Merck Sharp and Dohme Research Laboratories, Rahway, New Jersey 07065.
Garcia
M L
ML
Kaczorowski
G J
GJ
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000378:metabolism; D015220:Calcium Channels; D007700:Kinetics; D008978:Mollusk Venoms / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D013570:Synaptic Membranes / Q000378:metabolism*; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D008978:Mollusk Venoms; D017981:Receptors, Neurotransmitter; C053157:omega-conotoxin receptor; D020866:omega-Conotoxin GVIA