Abstract
Acute treatment of rat spinal cord-dorsal root ganglion cocultured neurons with 12-O-tetradecanoylphorbol 13-acetate (TPA), a known activator of protein kinase C, inhibited the dihydropyridine-sensitive voltage-dependent 45Ca2+ influx measured in these cells (IC50 of approximately 100 nM, 66% inhibition at 1 microM TPA). However, prolonged preincubation (24 h) of the cells with 100 nM TPA followed by extensive washing completely abolished, i.e., desensitized, the capacity of a second application of TPA to inhibit the activity of the voltage-dependent Ca2+ channels. Moreover, this treatment also abolished the inhibition of Ca2+ influx produced by kappa-opiate as well as by alpha 2-adrenergic and muscarinic receptor agonists. Substantial desensitization was already observed following a 1-h pretreatment with 100 nM TPA. In contrast to TPA, an inactive phorbol ester (4 beta-phorbol 13-acetate) did not affect the inhibition of the voltage-dependent Ca2+ influx by these receptor agonists. These results suggest that protein kinase C may have a role in the modulation of Ca2+ channels by kappa-opiate, alpha 2-adrenergic, and muscarinic receptor agonists.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
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3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / pharmacology*
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Analgesics / pharmacology
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Animals
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Calcium / metabolism
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Calcium Channels / drug effects
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Calcium Channels / physiology*
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Cell Communication
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Cells, Cultured
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Clonidine / pharmacology*
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Ganglia, Spinal / physiology*
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Kinetics
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Neurons / drug effects
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Neurons / physiology*
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Oxotremorine / pharmacology*
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Potassium / pharmacology
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Pyrrolidines / pharmacology*
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Rats
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Receptors, Adrenergic, alpha / drug effects
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Receptors, Adrenergic, alpha / physiology*
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Receptors, Muscarinic / drug effects
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Receptors, Muscarinic / physiology*
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Receptors, Opioid / drug effects
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Receptors, Opioid / physiology*
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Receptors, Opioid, mu
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Spinal Cord / physiology*
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Tetradecanoylphorbol Acetate / pharmacology*
Substances
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Analgesics
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Calcium Channels
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Pyrrolidines
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Receptors, Adrenergic, alpha
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Receptors, Muscarinic
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Receptors, Opioid
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Receptors, Opioid, mu
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Oxotremorine
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3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
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3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
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Clonidine
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Tetradecanoylphorbol Acetate
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Potassium
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Calcium