Actions of neomycin on neuronal L-, N-, and non-L/non-N-type voltage-sensitive calcium channel responses.
The effects of neomycin on neuronal voltage-sensitive calcium channel (VSCC) responses were investigated by evaluating its effects on calcium-dependent neuronal responses that are sensitive and insensitive to the N-type voltage-sensitive calcium channel antagonist omega-conotoxin GVIA and the L-type VSCC antagonist nitrendipine. Chick synaptosomal 45Ca2+ influx and K(+)-evoked release of [3H]norepinephrine from chick cortical brain slices were omega-conotoxin GVIA sensitive and nitrendipine insensitive, suggesting that these responses are mediated predominantly by N-type VSCC. The K(+)-evoked increase of intracellular calcium in cortical neurons and the K(+)-evoked release of [3H]norepinephrine from rat brain cortical slices was partially sensitive to omega-conotoxin GVIA and nitrendipine, suggesting that these responses are mediated by N-, L- and non-L/non-N-type VSCC. Rat synaptosomal 45Ca2+ influx and the K(+)-evoked release of [3H]D-aspartate from rat hippocampal slices were completely insensitive to omega-conotoxin GVIA and nitrendipine, suggesting that these responses were mediated predominantly by non-L/non-N-type VSCC. Neomycin caused a concentration-dependent and virtually complete inhibition of all response parameters, with IC50 values ranging from 90 to 400 microM. The results suggest that neomycin is a nonselective inhibitor of neuronal responses mediated by L-, N-, and non-L/non-N-type VSCC.
Keith
R A
RA
Department of Pharmacology, ICI Americas, Inc., Wilmington, DE 19897.
Mangano
T J
TJ
DeFeo
P A
PA
Horn
M B
MB
Salama
A I
AI
D000818:Animals; D001921:Brain / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects*; D002642:Chick Embryo; D008297:Male; D009355:Neomycin / Q000494:pharmacology*; D009568:Nitrendipine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D010456:Peptides, Cyclic; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D020866:omega-Conotoxin GVIA
D015220:Calcium Channels; D010456:Peptides, Cyclic; D020866:omega-Conotoxin GVIA; D009568:Nitrendipine; D009355:Neomycin; D011188:Potassium; D009638:Norepinephrine