Vasopressin stimulates pyruvate utilization through a Ca(2+)-dependent mechanism and lactate formation by a protein kinase C-dependent mechanism in isolated rat hepatocytes.
Vasopressin stimulates lactate production by hepatocytes from fed rats, an effect which has been attributed exclusively to Ca2+ activation of glycogenolysis. We provide evidence here for two further actions of vasopressin which affect lactate formation by rat hepatocytes. In the presence of 50 mM glucose, vasopressin inhibited lactate production by hepatocytes. The inhibition was relieved by the presence of alpha-cyano-4-hydroxycinnamate (alpha-CHC), which blocks mitochondrial pyruvate transport. This suggests that vasopressin stimulates pyruvate utilization in the presence of a high concentration of glucose. Epidermal growth factor (EGF), which also increases lactate formation by hepatocytes, did not similarly decrease lactate accumulation in the presence of high glucose, suggesting no stimulation of lactate and pyruvate utilization by this hormone. In cells depleted of Ca2+, vasopressin also stimulated lactate formation. Although vasopressin did not cause the apparent translocation of protein kinase C between cell spaces, phospholipase C treatment of hepatocytes did duplicate vasopressin stimulation of lactate formation, provided fatty acid oxidation was suppressed by the simultaneous presence of the inhibitor palmixorate. We conclude that three actions of vasopressin affect lactate and pyruvate formation: the calcium-linked activations of glycogenolysis and mitochondrial pyruvate utilization, and a stimulation of glycolysis likely mediated by protein kinase C.
Department of Nutrition, Case Western Reserve University, Mt. Sinai Medical Center, Cleveland, OH 44106-4198.
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D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003373:Coumaric Acids / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D007773:Lactates / Q000378:metabolism*; D019344:Lactic Acid; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D011773:Pyruvates / Q000378:metabolism*; D019289:Pyruvic Acid; D051381:Rats; D010738:Type C Phospholipases / Q000378:metabolism; D014667:Vasopressins / Q000494:pharmacology*
D003373:Coumaric Acids; D005227:Fatty Acids; D007773:Lactates; D011773:Pyruvates; D014667:Vasopressins; C007175:alpha-cyano-4-hydroxycinnamate; D019344:Lactic Acid; D004815:Epidermal Growth Factor; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D010738:Type C Phospholipases; D005947:Glucose; D002118:Calcium