Norepinephrine inhibits a Ca2+ current in rat sympathetic neurons via a G-protein.
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.
Schofield
G G
GG
Department of Physiology, Tulane University Medical School, New Orleans, LA 70112.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005728:Ganglia, Sympathetic / Q000187:drug effects* / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D037342:Pertussis Toxin; D051381:Rats; D011919:Rats, Inbred Strains; D013873:Thionucleotides / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D015220:Calcium Channels; D013873:Thionucleotides; D010566:Virulence Factors, Bordetella; D006153:Guanosine Diphosphate; D006165:Guanylyl Imidodiphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C023427:guanosine 5'-O-(2-thiodiphosphate); D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine; D009638:Norepinephrine