The polyamine spermine affects omega-conotoxin binding and function at N-type voltage-sensitive calcium channels.
1. The effects of the polyamines, spermine and spermidine on neuronal N-type voltage-sensitive calcium channels were investigated using the binding and function of the ligand omega-conotoxin GVIA (omega-CT). 2. Spermine and spermidine enhanced (EC50 approximately 0.16 and 0.45 microM) and, at higher concentrations, inhibited (IC50 of 9 and 240 microM) the binding of [125I]omega-CT to rat hippocampal synaptosomes. 3. Spermine and, less potently, spermidine inhibited the neurotransmitter-mediated, omega-CT-sensitive, electrical-field-stimulated contractile responses of the rat vas deferens. 4. The polyamines also inhibited the phenylephrine-evoked contractile responses of the vas deferens with the same rank order, consistent with a postsynaptic mechanism of inhibition. 5. However, pre-exposure to spermine prevented the irreversible inhibition of vas deferens twitch responses by omega-CT (previously found to be presynaptic). The prevention of inhibition by omega-CT demonstrates that the neuronal binding of spermine and omega-CT is mutually exclusive. Thus spermine (and presumably spermidine at higher concentrations) appears to modulate the actions of omega-CT at N-type voltage-sensitive calcium channels.
Pullan
L M
LM
ICI Pharmaceuticals Group, ICI Americas Inc., Wilmington, Delaware 19897.
Keith
R A
RA
LaMonte
D
D
Stumpo
R J
RJ
Salama
A I
AI
D000818:Animals; D015220:Calcium Channels / Q000378:metabolism* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000378:metabolism / Q000648:ultrastructure; D007457:Iodine Radioisotopes; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D010456:Peptides, Cyclic / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D013095:Spermidine / Q000494:pharmacology; D013096:Spermine / Q000494:pharmacology*; D013574:Synaptosomes / Q000378:metabolism / Q000648:ultrastructure; D014649:Vas Deferens / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D020866:omega-Conotoxin GVIA
D015220:Calcium Channels; D007457:Iodine Radioisotopes; D010456:Peptides, Cyclic; D013096:Spermine; D020866:omega-Conotoxin GVIA; D013095:Spermidine