Nicotine Increases Hepatic Oxygen Uptake in the Isolated Perfused Rat Liver by Inhibiting Glycolysis

Abstract

Nicotine influences energy metabolism, yet mechanisms remain unclear. Since the liver is one of the largest organs and performs many metabolic functions, the goal of this study was to determine whether nicotine would affect respiration and other metabolic functions in the isolated perfused liver. Infusion of 85 M nicotine caused a rapid 10% increase in oxygen uptake over basal values of 105 Ϯ 5 mol/g/h in perfused livers from fed rats, and an increase of 27% was observed with 850 M nicotine. Concomitantly, rates of glycolysis of 105 Ϯ 8 mol/g/h were decreased to 52 Ϯ 9 mol/g/h with nicotine, whereas ketone body production was unaffected. Nicotine had no effect on oxygen uptake in glycogen-depleted livers from 24-h fasted rats. Furthermore, addition of glucose to perfused livers from fasted rats partially restored the stimulatory effect of nicotine. Infusion of atractyloside, potassium cyanide, or glucagon blocked the nicotine-induced increase in respiration. Intracellular calcium was increased in isolated hepatocytes by nicotine, a phenomenon prevented by incubation of cells with d-tubocurarine, a nicotinic acetylcholine receptor antagonist. Respiration was also increased ϳ30% in hepatocytes isolated from fed rats by nicotine, whereas hepatocytes isolated from fasted rats showed little response. In the presence of N- [2-(pbromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89), an inhibitor of cyclic AMP-dependent protein kinase A, nicotine failed to stimulate respiration. These data support the hypothesis that inhibition of glycolysis by nicotine increases oxygen uptake due to an ADP-dependent increase in mitochondrial respiration.

Functional Promoter Polymorphisms Govern Differential Expression of HMG-CoA Reductase Gene in Mouse Models of Essential Hypertension

“…Are there functional nicotinic acetylcholine receptors (nAChRs) in these cell types to elicit nicotine-induced Hmgcr promoter stimulation? In isolated rat hepatocytes, nicotine increased intracellular calcium concentration and this phenomenon was blocked by d -tubocurarine, a nAChR antagonist [54]. A recent study also detected the presence of alpha-7 nAChRs in mouse liver by utilizing two carbon-11-labeled alpha-7 nAChR agonists [55].…”

Nicotine Increases Size and Severity of Experimental Choroidal Neovascularization

“…They are also widely expressed in peripheral non-neural cells, including hepatocytes, VSMCs, and ECs. 17,22,27,28 The tissue-specific differences in heterodimer combinations and expression have been studied in many tissues, but not in the choroid or retina. 26,27,29 -33 The function, ligands, and signaling cascades of extraneuronal nicotinic receptors are not well understood.…”

Regional metabolite levels and turnover in the awake rat brain under the influence of nicotine

“…Perhaps the richness of dopamine receptors in the thalamus contributes to the balance. Indeed, acute nicotine dosing has been reported to reduce glycolysis (Dewar et al. 2002), though those findings were in the liver.…”