Blockade by Neurotransmitter Antagonists of Veratridine-Activated Ion Channels in Neuronal Cell Lines |
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Authors: | Georg Reiser rea Günther Bernd Hamprecht |
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Institution: | Physiologisch-chemisches Institut der Universität Würzburg, Würzburg, F.R.G. |
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Abstract: | Abstract: The voltage-dependent Na+ ionophore of various neuronal cells is permeable not only to Na+ ions but also to guanidinium ions. Therefore, the veratridine-(or aconitine-) stimulated influx of 14C]guanidinium in neuroblastoma × glioma hybrid cells was measured to characterize the Na+ ionophore of these cells. Half-maximal stimulation of guanidinium uptake was seen at 30 μ M veratridine. At 1 m M guanidinium, the veratridine-stimulated uptake of guanidinium was lowered to 50% by approximately 60 m M Li+, Na+, or K+ and by a few millimolar Mn2+, Co2+, or Ni2+. The basal, as well as the veratridine-stimulated, uptake of guanidinium was inhibited by the cholinergic antagonists (+)-tubocurarine ( Ki = 50 to 500 n M ) and atropine ( Ki = 5 to 30 μ M ) and the adrenergic antagonists phentolamine ( Ki = 5 μ M ) and propranolol ( Ki = 60 μ M ). The specificity of the inhibitory effects of these agents is stressed by the ineffectiveness of various other neurotransmitter antagonists. However, the corresponding ionophore in neuroblastoma cells (clone N1E-115) seems to be regulated differently. While phentolamine and propranolol inhibit the veratridine-activated uptake as in the hybrid cells, (+)-tubocurarine and atropine exert only a slight effect. |
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Keywords: | Atropine Aconitine Neuroblastoma × glioma hybrid cells Phentolamine Propranolol Tubocurarine |
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