Neurotoxic aminoglycoside antibiotics are potent inhibitors of [125I]-Omega-Conotoxin GVIA binding to guinea-pig cerebral cortex membranes

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Abstract
[125I]-Omega-Conotoxin GVIA, a blocker of neuronal (N-type) calcium channels labelled 295 ± 121 fmol per mg protein of high affinity sites (apparent half-saturation at 1.5 to 2.5 pmol/1) in guinea-pig cerebral cortex membranes.Divalentcations (Cd2+ > Ni2+ > Co2+ > Ca2+ > Sr2+ = Ba2+ > Mg2+) and La3+ were potent inhibitors of Omega-Conotoxin GVIA binding, whereas monovalent cations (Na+, K+, Li+) were ineffective up to 50 mmol/1. Aminoglycosides (neomycin > gentamycin = tobramycin > streptomycin > amikacin > kanamycin) and polymyxin B also inhibited [1251I]-Omega-Conotoxin GVIA binding with IC50 values in the μmolar range. All other antibiotics tested were ineffective up to 1 mmol/1. With the exception of polymyxin B, which partially inhibited the binding of the 1,4-dihydropyridine (+)-[3H]PN 200–110 and of (−)-[3H]desmethoxyverapamil, the aminoglycosides and the other antibiotics had no effect on the L-type calcium channel labelling. It is suggested, that inhibition of neurotransmitter release by aminoglycosides is mediated via blockade of the N-type calcium channel to which [125I]-Omega-Conotoxin GVIA binds selectively in a quasi irreversible manner.