The mechanism of action of hepatic sympathetic nerves on ketone-body output from perfused rat liver. The effect of the interaction of noradrenaline with ATP on the release of beta-hydroxybutyrate.
The regulatory mechanism of ketone-body output by the hepatic sympathetic nerves was studied in rat liver perfused in situ. Enrichment of the perfusion medium with 1 mM octanoate increased the basal ketone-body output from the liver up to 1.5 mumol.min-1.g liver-1. Under these conditions, electrical stimulation of the hepatic nerves (20 V, 20 Hz, 2 ms) decreased the output of both acetoacetate and beta-hydroxybutyrate, and was accompanied by an accumulation of beta-hydroxybutyrate in the liver. The effects of nerve stimulation were inhibited by the alpha 1-antagonist bunazosin (10 microM). However, noradrenaline, a typical sympathetic neurotransmitter, at a concentration of 1 microM decreased the output of acetoacetate but did not affect beta-hydroxybutyrate output. Prostaglandin F2 alpha at a concentration of 10 microM produced an effect similar to treatment with noradrenaline, without a decrease in beta-hydroxybutyrate output. ATP at 50 microM, however, decreased the output of both acetoacetate and beta-hydroxybutyrate and increased the tissue concentration of beta-hydroxybutyrate, mimicking the effect of nerve stimulation. Moreover, in the presence of 0.2 microM ATP, a concentration that produced neither metabolic nor hemodynamic changes, noradrenaline (1 microM) was shown to decrease the beta-hydroxybutyrate output. These results indicate the possible involvement of ATP in the action of hepatic sympathetic nerves on beta-hydroxybutyrate output from the liver, presumably through its interaction with noradrenaline.
Department of Medical Biochemistry, Ehime University School of Medicine, Japan.
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Yamamoto
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Iwai
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Kimura
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Shimazu
D020155:3-Hydroxybutyric Acid; D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D015237:Dinoprost / Q000494:pharmacology; D004558:Electric Stimulation; D006885:Hydroxybutyrates / Q000378:metabolism*; D007657:Ketone Bodies / Q000378:metabolism*; D008099:Liver / Q000294:innervation* / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D013498:Suramin / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000502:physiology*
D006885:Hydroxybutyrates; D007657:Ketone Bodies; D013498:Suramin; D000255:Adenosine Triphosphate; D015237:Dinoprost; D000241:Adenosine; D020155:3-Hydroxybutyric Acid; D009638:Norepinephrine