Norepinephrine inhibits a Ca2+ current in rat sympathetic neurons via a G-protein

Eur J Pharmacol. 1991 Jul 12;207(3):195-207. doi: 10.1016/0922-4106(91)90031-c.


The effects of norepinephrine on a Ca2+ current from acutely isolated and short-term (24 h) cultured adult rat superior cervical ganglion neurons were studied using the whole-cell variant of the patch-clamp technique. Norepinephrine produced a rapid, reversible and concentration-dependent reduction of the Ca2+ current. Accurately timed applications of norepinephrine (3 microM) showed that the development of Ca2+ current inhibition was delayed by up to 11 s after application of norepinephrine. Internal 500 microM guanylyl-imidodiphosphate (Gpp(NH)p) or guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma-S) decreased the Ca2+ current amplitude and induced a biphasic rising phase of the Ca2+ current. Under these conditions, the reduction of Ca2+ current amplitude by 3 microM norepinephrine was virtually abolished when compared with cells dialysed with GTP-containing internal solutions. Internal dialysis with solutions containing 2 mM guanosine-5'-O-(2-thiodiphosphate) (GDP-beta-S) increased the Ca2+ current amplitude and reduced the inhibition produced by 3 microM norepinephrine compared to cells dialysed with control internal solution. Treatment with 200 ng/ml pertussis toxin for 12-16 h greatly reduced the norepinephrine-induced Ca2+ current inhibition. Internal dialysis with solutions containing 500 microM cyclic adenosine 3',5'-monophosphate (cyclic AMP) and 3-isobutyl-1-methylxanthine had no significant effect on either the Ca2+ current inhibition by norepinephrine or the Ca2+ current amplitude. These results suggest that norepinephrine blocks a Ca2+ current in adult rat superior cervical ganglion neurons via a pertussis toxin-sensitive G-protein which is independent of intracellular cyclic AMP.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 1-Methyl-3-isobutylxanthine / pharmacology
  • Animals
  • Calcium / metabolism*
  • Calcium Channels / drug effects*
  • Calcium Channels / metabolism
  • Cells, Cultured
  • Cyclic AMP / pharmacology
  • GTP-Binding Proteins / metabolism*
  • Ganglia, Sympathetic / drug effects*
  • Ganglia, Sympathetic / metabolism
  • Guanosine 5'-O-(3-Thiotriphosphate) / pharmacology
  • Guanosine Diphosphate / analogs & derivatives
  • Guanosine Diphosphate / pharmacology
  • Guanylyl Imidodiphosphate / pharmacology
  • Male
  • Neurons / drug effects
  • Neurons / metabolism
  • Norepinephrine / pharmacology*
  • Pertussis Toxin
  • Rats
  • Rats, Inbred Strains
  • Thionucleotides / pharmacology
  • Virulence Factors, Bordetella / pharmacology


  • Calcium Channels
  • Thionucleotides
  • Virulence Factors, Bordetella
  • Guanosine Diphosphate
  • Guanylyl Imidodiphosphate
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • guanosine 5'-O-(2-thiodiphosphate)
  • Cyclic AMP
  • Pertussis Toxin
  • GTP-Binding Proteins
  • Calcium
  • 1-Methyl-3-isobutylxanthine
  • Norepinephrine