Increase in glucose and lactate output and perfusion resistance by stimulation of hepatic nerves in isolated perfused rat liver: role of alpha 1-, alpha 2-, beta 1- and beta 2-receptors.
Rat liver was perfused in situ via the portal vein without recirculation: 1) Electrical stimulation of the nerve bundles around hepatic artery and portal vein increased glucose and lactate output, reduced flow and caused an overflow of noradrenaline into the hepatic vein. The alpha-agonist phenylephrine also augmented glucose and lactate output and lowered flow with an ED50 of about 1 microM, while the beta-agonist isoproterenol increased glucose output but reduced lactate output with an ED50 of about 0.2 microM and left flow unaltered. 2) The alpha 1-receptor antagonist prazosin (KI at alpha 1-sites approximately 1 nM, at alpha 2-sites approximately 100 nM) inhibited the nerve stimulation-dependent increase in glucose and lactate output and reduction of flow with an ID50 of about 1 nM, while the alpha 2-receptor antagonist yohimbine (KI at alpha 2-sites approximately 10 nM, at alpha 1-sites approximately 1500 nM) was inhibitory only with an ID50 of about 400 nM. 10 nM prazosin clearly reduced the nerve actions, completely blocked the effects of 1 microM phenylephrine and left the effects of 0.2 microM isoproterenol unaltered. 10 nM yohimbine did not affect the nerve actions nor the effects of phenylephrine or isoproterenol. 3) The beta 1-receptor antagonist metoprolol (KI at beta 1-sites approximately 100 nM, at beta 2-sites approximately 1.2 microM) at 10 microM concentrations did not interfere with the nerve stimulation-dependent increase in glucose and lactate output or the decrease in flow. It did not have any specific alpha-antagonistic influence either on the changes brought about by 1 microM phenylephrine; however, it blocked the beta 2-mediated increase in glucose output by isoproterenol.(ABSTRACT TRUNCATED AT 250 WORDS)
Ulken
V
V
Institut für Biochemie, Fachbereich Medizin, Georg-August-Universität, Göttingen.
Püschel
G P
GP
Jungermann
K
K
D000818:Animals; D002078:Butoxamine / Q000494:pharmacology; D004558:Electric Stimulation; D005947:Glucose / Q000378:metabolism*; D006439:Hemodynamics / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology*; D007700:Kinetics; D007773:Lactates / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D008297:Male; D008790:Metoprolol / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D010477:Perfusion / Q000379:methods; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology*
D007773:Lactates; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D002078:Butoxamine; D010656:Phenylephrine; D015016:Yohimbine; D008790:Metoprolol; D005947:Glucose; D007545:Isoproterenol; D009638:Norepinephrine; D011224:Prazosin