VIP inhibits N-type Ca2+ channels of sympathetic neurons via a pertussis toxin-insensitive but cholera toxin-sensitive pathway.
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.
Zhu
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Y
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta 30912-2300.
Ikeda
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SR
D000818:Animals; D000068438:Brimonidine Tartrate; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000145:classification / Q000378:metabolism* / Q000502:physiology; D002772:Cholera Toxin / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004594:Electrophysiology; D019204:GTP-Binding Proteins / Q000502:physiology; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D037342:Pertussis Toxin; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015290:Second Messenger Systems; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D011810:Quinoxalines; D010566:Virulence Factors, Bordetella; D014660:Vasoactive Intestinal Peptide; D000068438:Brimonidine Tartrate; D002772:Cholera Toxin; D037342:Pertussis Toxin; D017868:Cyclic AMP-Dependent Protein Kinases; D019204:GTP-Binding Proteins