Abstract
The best characterized Ca2+ channel modulation in mammalian sympathetic neurons is an inhibition of N-type channels via a pertussis toxin (PTX)-sensitive heterotrimeric G protein. Here, we show that vasoactive intestinal polypeptide (VIP), an abundant neuropeptide in the PNS and CNS, inhibited N-type Ca2+ channels in rat sympathetic neurons in a voltage-dependent, membrane-delimited manner. The effect of VIP was insensitive to PTX but was attenuated by cholera toxin or anti-Gs alpha antibodies. VIP-mediated inhibition was independent of cAMP-dependent protein kinase A (PKA). The results provide evidence for a new signal transduction pathway in which N-type Ca2+ channel modulation requires activation of Gs alpha but is independent of PKA-mediated phosphorylation.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Brimonidine Tartrate
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Calcium Channel Blockers / pharmacology*
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Calcium Channels / classification
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Calcium Channels / metabolism*
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Calcium Channels / physiology
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Cholera Toxin / pharmacology*
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Cyclic AMP-Dependent Protein Kinases / metabolism
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Electrophysiology
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GTP-Binding Proteins / physiology
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Ganglia, Sympathetic / cytology
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Ganglia, Sympathetic / metabolism*
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Neurons / metabolism
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Pertussis Toxin*
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Quinoxalines / pharmacology
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Rats
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Rats, Wistar
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Second Messenger Systems
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Vasoactive Intestinal Peptide / pharmacology*
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Virulence Factors, Bordetella / pharmacology*
Substances
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Calcium Channel Blockers
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Calcium Channels
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Quinoxalines
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Virulence Factors, Bordetella
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Vasoactive Intestinal Peptide
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Brimonidine Tartrate
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Cholera Toxin
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Pertussis Toxin
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Cyclic AMP-Dependent Protein Kinases
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GTP-Binding Proteins