Failure of omega-conotoxin to block L-channels associated with [3H]5-HT release in rat brain slices.
The effects of the mixed N- and L-type voltage-sensitive calcium channel (VSCC) antagonist, omega-conotoxin GVIA and the L-type VSCC agonist Bay K-8644 on calcium-dependent, potassium evoked release of [3H]5-hydroxtryptamine ([3H]5-HT) were investigated in slices of rat hippocampus. Bay K-8644 (1 microM) enhanced, whilst omega-conotoxin (10-30 nM) attenuated, but did not abolish, evoked release of [3H]5-HT. The facilitatory actions of Bay K-8644 on evoked release were unaffected by concentrations of omega conotoxin that significantly inhibited [3H]5-HT release. The experiments indicate that concentrations of omega-conotoxin which inhibit neurotransmitter release by blockade of N-type VSCC, may leave L-type calcium channel activity unaffected.
Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, U.K.
I
I
Rijnhout
D R
DR
Hill
D N
DN
Middlemiss
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000493:pharmacokinetics*; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D010456:Peptides, Cyclic; D012701:Serotonin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D020866:omega-Conotoxin GVIA