The inhibition of [125I]omega-conotoxin GVIA binding to neuronal membranes by neomycin may be mediated by a GTP-binding protein.
omega-Conotoxin GVIA (omega-CT) has been reported to block calcium currents at the L- and N-type calcium channels. In neuronal membranes omega-CT, and the aminoglycoside antibiotic neomycin, have been shown to inhibit [125I]omega-CT binding, presumably acting at the N-type calcium channel. We demonstrate here that the concentration curve for neomycin sulfate inhibition of [125I]omega-CT binding is shifted to the right by GTP analogues or fluoride, increasing the IC50 for neomycin. [125I]omega-CT binding is unaffected by these agents and in competition studies the potency of omega-CT, Ca2+, or La3+ is not modulated by GTP analogues or fluoride. These results indicate that the inhibition of [125I]omega-CT binding by neomycin may be mediated by a GTP binding protein.
Stumpo
R J
RJ
Department of Pharmacology, ICI Pharmaceuticals Group, ICI Americas Inc., Wilmington, DE 19897.
Pullan
L M
LM
Salama
A I
AI
D000495:Allosteric Site; D000818:Animals; D002121:Calcium Channel Blockers / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D009355:Neomycin / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010456:Peptides, Cyclic; D020866:omega-Conotoxin GVIA; D019204:GTP-Binding Proteins; D009355:Neomycin