title: Characterization of the effects of omega-conotoxin GVIA on the responses of voltage-sensitive calcium channels.
abstract: 1. omega-conotoxin GVIA (omega-CT) caused a potent (IC50 approximately 2nM) but less than maximal (55%) inhibition of [3H]-noradrenaline release from cortical brain slices induced by K+. At 0.1 microM, omega-CT inhibited [3H] gamma-aminobutyric acid (GABA) and [3H]-acetylcholine release by approximately 40%. 2. K+-evoked [3H]-noradrenaline release from cortical brain slices was also characterized with respect to the effects of PN 200-110 (dihydropyridine L-channel antagonist), BAY K8644 (L-channel VSCC agonist), and Cd++ (an inorganic L- and N-channel antagonist). 10 microM Cd++ and 1 microM PN 200-110 inhibited K+-evoked [3H]-noradrenaline release by 52% and 17%, respectively. 10 microM Bay K 8644 enhanced K+-evoked [3H]-noradrenaline release by 22%, and this enhancement was blocked by 1 microM PN 200-110. 3. omega-CT caused a near-maximal inhibition of the electrically evoked twitch responses of the rat vas deferens (IC50 approximately 10 nM) and guinea-pig ileum (IC50 approximately 60 nM), but had no effect on the postjunctional contractile responses of noradrenaline (vas deferens) or carbachol (ileum). At concentrations as high as 1 microM, omega-CT had no effect on the K+-induced contraction of the rat aorta. 4. Neither the equilibrium binding of [3H]-(+)-PN 200-110 nor the allosteric regulation of [3H]-(+)-PN 200-110 binding by tiapamil or diltiazem were altered by omega-CT (0.1 microM). 5. These observations support the notion that the N-type voltage-sensitive calcium channel plays a major role in coupling neuronal excitation with neurotransmitter release.
authors.affiliation: Department of Pharmacology, ICI Pharmaceuticals Group, Wilmington, Delaware 19897.
authors.forename: R A
authors.initials: RA
authors.lastname: Keith
authors.forename: T J
authors.initials: TJ
authors.lastname: Mangano
authors.forename: M A
authors.initials: MA
authors.lastname: Pacheco
authors.forename: A I
authors.initials: AI
authors.lastname: Salama
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects*; D004558:Electric Stimulation; D006168:Guinea Pigs; D066298:In Vitro Techniques; D017275:Isradipine; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D008978:Mollusk Venoms / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000378:metabolism; D010069:Oxadiazoles / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology; D020866:omega-Conotoxin GVIA
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D008978:Mollusk Venoms; D018377:Neurotransmitter Agents; D010069:Oxadiazoles; D005680:gamma-Aminobutyric Acid; D020866:omega-Conotoxin GVIA; D000109:Acetylcholine; D011188:Potassium; D017275:Isradipine