Effects of adrenaline on glucose and glutamine metabolism and superoxide production by rat neutrophils

Abstract

Despite the large body of information on the role of corticosteroids in regulating lymphocyte and phagocyte function, the role of the hormone adrenaline in immunoregulation is an under-investigated topic. The present study has addressed the effects of adrenaline on the rates of utilization and oxidation of glucose and glutamine, the phagocytic capacity and the rate of superoxide production by rat neutrophils. Incubation of rat neutrophils in the presence of 50 microM adrenaline caused a marked elevation in glucose metabolism, an effect that could be blocked by propranolol. Adrenaline caused a partial inhibition of glutamine utilization by neutrophils, an effect that was also blocked by propranolol. These effects of adrenaline could be mimicked by 100 microM dibutyryl cAMP. Phosphate-dependent glutaminase activity was significantly elevated in neutrophils incubated in the presence of 50 microM adrenaline or 100 microM dibutyryl cAMP for 1 h, whereas glutamine oxidation was significantly depressed (P<0.05) under these conditions. The elevation in enzyme activity was only partially blocked by propranolol. The phagocytic activity of rat neutrophils was not altered by adrenaline in the presence of either glucose or glutamine. The rate of phorbol 12-myristate 13-acetate-induced superoxide production in the presence of glucose was potently reduced by the addition of 5 nM or 50 microM adrenaline. This effect could be mimicked by dibutyryl cAMP. However, when rat neutrophils were incubated in the presence of glutamine plus adrenaline (5 nM or 50 microM), the rate of superoxide production was only marginally reduced. These findings support the proposition that adrenaline may deviate the flux of glucose from the NADPH-producing pentose phosphate pathway, thus reducing substrate availability for the superoxide-generating NADPH oxidase. However, glutamine metabolism may still give rise to substantial quantities of NADPH from the glutaminolysis pathway. We postulate that glutamine metabolism may thus provide a protective mechanism against the inhibitory effect of adrenaline on superoxide production by neutrophils.

Evidence that glutamine is involved in neutrophil function

“…In a previous study, we found that glutamine may give rise to substantial quantities of NADPH for superoxide production in rat neutrophils. 10 Similar observations have been obtained in neutrophils from postoperative patients. 11 This fact explains the observations that glutamine enhances the bactericidal function of neutrophils from normal patients and those suffering from burns.…”

Time sequence of changes in the responsiveness of glycogen breakdown to adrenergic agonists in perfused liver of rats with insulin-induced hypoglycemia

“…Cyclic AMP is known to be the second messenger of ß-adrenergic receptors (23). Thus, due to the fact that the most pronounced changes in glycogen breakdown were observed for isoproterenol, in the second set of experiments the effect of dibutyryl cyclic AMP was tested.…”

Effect of dexamethasone on neutrophil metabolism

“…The activity of glucose-6phosphate dehydrogenase (G6PDH; EC 1.1.1.49) was determined as previously described. 4,10 The extraction medium contained 50 mM Tris-HCl and 1 mM EDTA; the final pH was 8.0. For the enzyme assay, Triton X-100 0.05% (v/v) was added to the assay system to complete the extraction of the enzyme.…”

“…Evidence has been obtained that glucose metabolism is required both for new membrane synthesis during active periods of phagocytosis and for production of NADPH (through the pentose phosphate pathway). 5,6 The metabolism of glutamine has been associated with phagocytosis 7,8 and production of O :À 2 , [9][10][11] and TNF 12 by neutrophils.…”