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        Rank-order inhibition by ω-conotoxins in human and animal autonomic nerve preparations

        Author
        Sanger, G.
        Ellis, E.S.
        Harries, M.
        Tilford, N.S.
        Wardle, K.A.
        Benham, C.D.
        Attention
        2299/3505
        Abstract
        The inhibitory effects of the ω-conotoxins GVIA, MVIIA and MVIIC on electrically-evoked, tetrodotoxin (10−7 M)-sensitive, autonomic nerve activity were studied using human, rat or guinea-pig vas deferens and intestinal tissues. In each preparation from each species, nM concentrations of ω-conotoxins GVIA and MVIIA prevented the neuronally-mediated contractions, whereas ω-conotoxin MVIIC was either markedly less potent (IC50's 1.4 or 2.9 log units more than for ω-conotoxin GVIA in guinea-pig ileum and rat vas deferens, respectively) or was without significant activity (human vas deferens, human Taenia coli) when tested at similar concentrations. In contrast the differences in potency between ω-conotoxins GVIA and MVIIC were considerably less when assayed directly on Ca2+ channel currents evoked from rat superior cervical ganglion neurons in culture (approximately 0.1 log unit difference) and from a stable cell line expressing rat α1B, α2δ, β1b Ca2+ channel subunits (approximately 0.9 log unit). These different rank-orders of inhibitory activity of the conotoxins support the suggestion that there are pharmacologically distinct N-type Ca2+ channels in the peripheral nervous system, and that this tissue-dependent difference is seen in man.
        Publication date
        2000
        Published in
        European Journal of Pharmacology
        Published version
        https://doi.org/10.1016/S0014-2999(99)00830-4
        Other links
        http://hdl.handle.net/2299/3505
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