Characterization of the alpha-adrenergic stimulation of hepatic respiration.
The alpha-adrenergic agonist phenylephrine induces a biphasic stimulation of respiration in perfused isolated rat liver. The first phase, of rapid onset and short duration, is paralleled by increased glycogenolysis, glycolysis, and NAD redox potential. The second phase lasts for as long as the alpha-agonist is present and is accompanied by increased gluconeogenic flux. Only the second phase of sustained increased respiration is clearly dependent on extracellular Ca2+. In contrast, normal respiratory responses were obtained under Ca2+-loading conditions or in the presence of the Ca2+ ionophore A23187, indicating that the alpha-adrenergic action on respiration is not simply mediated by its ability to increase the cytosolic Ca2+ concentration. No stimulation of gluconeogenesis is observed in the absence of a sustained increase of respiration. However, it is not energy support that leads to the stimulation of glucose production. The adrenergic response is influenced by the nutritional status of the animal and the availability of oxidizable fuels. In livers from starved animals, the alpha-adrenergic respiratory response is abolished when long chain fatty acid oxidation is prevented by the addition of tetradecylglycidate. In the presence of pyruvate the respiratory response is partially restored. It is concluded that increased beta-oxidation is not mandatory for the alpha-adrenergic stimulation of respiration; however, maximal respiratory responses are obtained only when fatty acid oxidation is allowed to proceed. The latter finding appears to be the result of a limited flux through the tricarboxylic acid cycle when long chain fatty acid oxidation is impeded, secondary to a limiting acetyl CoA supply.
Endocrine Physiology Unit, Centro de Investigaciones Biológicas, CSIC, Madrid, Spain.
C
C
González-Manchón
J M
JM
Saz
M S
MS
Ayuso
R
R
Parrilla
D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism; D005943:Gluconeogenesis / Q000187:drug effects; D006019:Glycolysis / Q000187:drug effects; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D009752:Nutritional Status; D010084:Oxidation-Reduction / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects*; D010477:Perfusion; D010656:Phenylephrine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D005227:Fatty Acids; D010656:Phenylephrine; D002118:Calcium