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

Summary 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 molar 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.Abbreviations B _max maximum capacity of binding sites - MTL maximum therapeutic level Send offprint requests to H. Glossmann