title: The action of p-synephrine on hepatic carbohydrate metabolism and respiration occurs via both Ca(2+)-mobilization and cAMP production.
abstract: Citrus aurantium extracts, which contain large amounts of p-synephrine, are widely used for weight loss purposes and as appetite suppressants. In the liver, C. aurantium (bitter orange) extracts affect hemodynamics, carbohydrate metabolism, and oxygen uptake. The purpose of the present work was to quantify the action of p-synephrine and also to obtain indications about its mechanism of action, a task that would be difficult to accomplish with C. aurantium extracts due to their rather complex composition. The experimental system was the isolated perfused rat liver. p-Synephrine significantly stimulated glycogenolysis, glycolysis, gluconeogenesis, and oxygen uptake. The compound also increased the portal perfusion pressure and the redox state of the cytosolic NAD(+)/NADH couple. A Ca(2+)-dependency for both the hemodynamic and the metabolic effects of p-synephrine was found. p-Synephrine stimulated both cAMP overflow and the initial Ca(2+) release from the cellular stores previously labeled with (45)Ca(2+). The metabolic and hemodynamic actions of p-synephrine were strongly inhibited by α-adrenergic antagonists and moderately affected by β-adrenergic antagonists. The results allow to conclude that p-synephrine presents important metabolic and hemodynamic effects in the liver. These effects can be considered as both catabolic (glycogenolysis) and anabolic (gluconeogenesis), they are mediated by both α- and β-adrenergic signaling, require the simultaneous participation of both Ca(2+) and cAMP, and could be contributing to the overall stimulation of metabolism that usually occurs during weight loss periods.
authors.affiliation: Department of Biochemistry, University of Maringá, Avenida Colombo 5790, Maringá, 87020900, Brazil.
authors.forename: Andrea Luiza
authors.initials: AL
authors.lastname: de Oliveira
authors.forename: Jurandir Fernando
authors.initials: JF
authors.lastname: Comar
authors.forename: Anacharis Babeto
authors.initials: AB
authors.lastname: de Sá-Nakanishi
authors.forename: Rosane Marina
authors.initials: RM
authors.lastname: Peralta
authors.forename: Adelar
authors.initials: A
authors.lastname: Bracht
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D058673:Adrenergic beta-3 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D050260:Carbohydrate Metabolism / Q000187:drug effects*; D002957:Citrus / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis; D005943:Gluconeogenesis / Q000187:drug effects; D050261:Glycogenolysis / Q000187:drug effects; D006019:Glycolysis / Q000187:drug effects; D008099:Liver / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D013578:Synephrine / Q000494:pharmacology*; D015016:Yohimbine / Q000494:pharmacology
chemical_list: C097869:3-(2-ethylphenoxy)-1-(1,2,3,4-tetrahydronaphth-1-ylamino)-2-propanol oxalate; D058668:Adrenergic alpha-1 Receptor Antagonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D058673:Adrenergic beta-3 Receptor Antagonists; D010936:Plant Extracts; D011412:Propanolamines; D015016:Yohimbine; D019289:Pyruvic Acid; D011433:Propranolol; D000242:Cyclic AMP; D013578:Synephrine; D002118:Calcium; D011224:Prazosin