Role of extracellular calcium in the metabolic and hemodynamic actions of sympathetic nerve stimulation, noradrenaline and prostaglandin F2 alpha in perfused rat liver. Differential inhibition by nifedipine and verapamil.
In perfused rat liver hepatic nerve stimulation (10 Hz, 2 ms) caused an increase in glucose and lactate output, a decrease in flow and an overflow of noradrenaline into the hepatic vein. Noradrenaline (1 microM) (NA) and prostaglandin F2 alpha (5 microM) (PGF2 alpha), which are implicated as mediators of nerve action, elicited similar effects. 1) All actions of nerve stimulation and the hemodynamic but not the metabolic effects of noradrenaline and PGF2 alpha were largely dependent on extracellular calcium. 2) The dihydropyridine type calcium antagonist nifedipine (5 microM) inhibited the hemodynamic but not the metabolic actions of nerve stimulation, NA and PGF2 alpha, while the phenylalkylamine type calcium antagonist verapamil (5 microM) had no effect. These findings allow the following conclusions: Calcium influx into I nerve endings, necessary for the release of neurotransmitter, II parenchymal cells, for the display of metabolic effects induced by nerve stimulation, and III the actions of NA and PGF2 alpha, do not appear to be mediated by the normal affinity nifedipine- or the verapamil-sensitive channels. Calcium influx into vascular smooth muscle and/or endothelial cells for the display of hemodynamic action induced by nerve stimulation and the NA and PGF2 alpha effects, appear to occur through nifedipine-sensitive but verapamil-insensitive channels.
Athari
A
A
Fachbereich Medizin, Georg-August-Universität, Göttingen, Germany.
Jungermann
K
K
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015237:Dinoprost / Q000494:pharmacology*; D004558:Electric Stimulation; D005947:Glucose / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D008099:Liver / Q000294:innervation / Q000378:metabolism*; D008102:Liver Circulation / Q000187:drug effects; D008297:Male; D009411:Nerve Endings / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013564:Sympathetic Nervous System / Q000502:physiology*; D014700:Verapamil / Q000494:pharmacology
D007773:Lactates; D015237:Dinoprost; D014700:Verapamil; D009543:Nifedipine; D005947:Glucose; D002118:Calcium; D009638:Norepinephrine