Häussinger D, Sies H
Biochem J. 1984 Aug 1;221(3):651-8. doi: 10.1042/bj2210651.
Addition of phenylephrine to isolated perfused rat liver is followed by an increased 14CO2 production from [1-14C]glutamate, [1-14C]glutamine, [U-14C]proline and [3-14C]pyruvate, but by a decreased 14CO2 production from [1-14C]pyruvate. Simultaneously, there is a considerable decrease in tissue content of 2-oxoglutarate, glutamate and citrate. Stimulation of 14CO2 production from [1-14C]glutamate is also observed in the presence of amino-oxyacetate, suggesting a stimulation of glutamate dehydrogenase and 2-oxoglutarate dehydrogenase fluxes by phenylephrine. Inhibition of pyruvate dehydrogenase flux by phenylephrine is due to an increased 2-oxoglutarate dehydroxygenase flux. Phenylephrine stimulates glutaminase flux and inhibits glutamine synthetase flux to a similar extent, resulting in an increased hepatic glutamine uptake. Whereas the effects of NH4+ ions and phenylephrine on glutaminase flux were additive, activation of glutaminase by glucagon was considerably diminished in the presence of phenylephrine. The reported effects are largely overcome by prazosin, indicating the involvement of alpha-adrenergic receptors in the action of phenylephrine. It is concluded that stimulation of gluconeogenesis from various amino acids by phenylephrine is due to an increased flux through glutamate dehydrogenase and the citric acid cycle.
向离体灌注的大鼠肝脏中添加去氧肾上腺素后，[1-¹⁴C]谷氨酸、[1-¹⁴C]谷氨酰胺、[U-¹⁴C]脯氨酸和[3-¹⁴C]丙酮酸的¹⁴CO₂生成增加，但[1-¹⁴C]丙酮酸的¹⁴CO₂生成减少。同时，2-氧代戊二酸、谷氨酸和柠檬酸的组织含量显著降低。在氨基氧乙酸存在的情况下，也观察到[1-¹⁴C]谷氨酸的¹⁴CO₂生成受到刺激，这表明去氧肾上腺素刺激了谷氨酸脱氢酶和2-氧代戊二酸脱氢酶的通量。去氧肾上腺素对丙酮酸脱氢酶通量的抑制是由于2-氧代戊二酸脱氢酶通量增加。去氧肾上腺素刺激谷氨酰胺酶通量并在相似程度上抑制谷氨酰胺合成酶通量，导致肝脏谷氨酰胺摄取增加。虽然NH₄⁺离子和去氧肾上腺素对谷氨酰胺酶通量的作用是相加的，但在去氧肾上腺素存在的情况下，胰高血糖素对谷氨酰胺酶的激活作用显著减弱。哌唑嗪在很大程度上克服了所报道的这些作用，表明α-肾上腺素能受体参与了去氧肾上腺素的作用。得出的结论是，去氧肾上腺素对各种氨基酸糖异生的刺激是由于通过谷氨酸脱氢酶和柠檬酸循环的通量增加。
