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

[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/l) in guinea-pig cerebral cortex membranes. Divalent cations (Cd2+ greater than Ni2+ greater than Co2+ greater than Ca2+ greater than Sr2+ = Ba2+ greater than Mg2+) and La3+ were potent inhibitors of Omega-Conotoxin GVIA binding, whereas monovalent cations (Na+, K+, Li+) were ineffective up to 50 mmol/l. Aminoglycosides (neomycin greater than gentamycin = tobramycin greater than streptomycin greater than amikacin greater than kanamycin) and polymyxin B also inhibited [125I]-Omega-Conotoxin GVIA binding with IC50 values in the mumolar range. All other antibiotics tested were ineffective up to 1 mmol/l. 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.