Proadrenomedullin NH2-terminal 20 peptide inhibits the voltage-gated Ca2+ channel current through a pertussis toxin-sensitive G protein in rat pheochromocytoma-derived PC 12 cells.
The effect of proadrenomedullin NH2-terminal 20 peptide (PAMP) on the voltage-gated Ca2+ channel current was investigated using the perforated whole-cell clamp technique on NGF-treated PC12 cells. PAMP inhibited the Ba2+ current through N-type Ca2+ channels in a concentration dependent manner. Injection of GDPbetaS into the cell abolished the inhibition while injection of GTPgammaS into the cell made the inhibition irreversible, indicating that the PAMP-induced inhibition of the voltage-gated Ca2+ channel was mediated by a G protein. The inhibition was abolished by pretreating the cells with pertussis toxin, indicating that a pertussis toxin-sensitive G protein was involved in the signal transduction mechanism of PAMP. The present study revealed that the inhibition of catecholamine secretion from sympathetic nerve endings by PAMP could be explained by the inhibition of N-type Ca2+ channels, which was mediated by pertussis toxin-sensitive G protein.
Takano
K
K
Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Japan.
Yamashita
N
N
Fujita
T
T
D053607:Adrenomedullin; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects*; D004553:Electric Conductivity; D019204:GTP-Binding Proteins / Q000187:drug effects*; D015640:Ion Channel Gating / Q000187:drug effects*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides; D037342:Pertussis Toxin; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000959:Antihypertensive Agents; D015220:Calcium Channels; D010446:Peptide Fragments; D010455:Peptides; D011506:Proteins; D010566:Virulence Factors, Bordetella; D053607:Adrenomedullin; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins