Nervous control of liver metabolism and hemodynamics

Gardemann, Andreas; Püschel, Gerd P.; Jungermann, Kurt

doi:10.1007/978-3-642-78046-2_12

Cited by 20 publications

(33 citation statements)

References 108 publications

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“…[34][35][36][37][38] Although the enterohepatic circulation was interrupted, the bile acid pool was maintained by continuous infusion of Na ϩ -taurocholate at a nonsaturating rate. 39 Because previous studies have shown minimal effects of secretin in normal rats, 21,23 in contrast with the significant effects observed in rats with bile ductular cell proliferation, 23,24 high doses of the hormone were tried (Fig.…”

Section: Discussionmentioning

confidence: 99%

Bicarbonate-rich choleresis induced by secretin in normal rat is taurocholate-dependent and involves AE2 anion exchanger

et al. 2006

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Canalicular bile is modified along bile ducts through reabsorptive and secretory processes regulated by nerves, bile salts, and hormones such as secretin. Secretin stimulates ductular cystic fibrosis transmembrane conductance regulator (CFTR)-dependent Cl ؊ efflux and subsequent biliary HCO 3 ؊ secretion, possibly via Cl ؊ /HCO 3 ؊ anion exchange (AE). However, the contribution of secretin to bile regulation in the normal rat, the significance of choleretic bile salts in secretin effects, and the role of Cl ؊ /HCO 3 ؊ exchange in secretin-stimulated HCO 3 ؊ secretion all remain unclear. Here, secretin was administered to normal rats with maintained bile acid pool via continuous taurocholate infusion. Bile flow and biliary HCO 3 ؊ and Cl ؊ excretion were monitored following intrabiliary retrograde fluxes of saline solutions with and without the Cl ؊ channel inhibitor 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) or the Cl ؊ /HCO 3 ؊ exchange inhibitor 4,4 -diisothiocyanatostilbene-2,2 -disulfonic acid (DIDS). Secretin increased bile flow and biliary excretion of HCO 3 ؊ and Cl ؊ . Interestingly, secretin effects were not observed in the absence of taurocholate. Whereas secretin effects were all blocked by intrabiliary NPPB, DIDS only inhibited secretin-induced increases in bile flow and HCO 3 ؊ excretion but not the increased Cl ؊ excretion, revealing a role of biliary Cl ؊ /HCO 3 ؊ exchange in secretininduced, bicarbonate-rich choleresis in normal rats. Finally, small hairpin RNA adenoviral constructs were used to demonstrate the involvement of the Na ؉ -independent anion exchanger 2 (AE2) through gene silencing in normal rat cholangiocytes. AE2 gene silencing caused a marked inhibition of unstimulated and secretin-stimulated Cl ؊ /HCO 3 ؊ exchange. In conclusion, maintenance of the bile acid pool is crucial for secretin to induce bicarbonate-rich choleresis in the normal rat and that this occurs via a chloride-bicarbonate exchange process consistent with AE2 function. (HEPATOLOGY 2006;43:266-275.) S ecretin is known to induce bicarbonate-rich hydrocholeresis in many animal species. 1-7 Its interaction with a G-protein-coupled receptor selectively localized to the epithelial bile duct cells 8 results in increased intracellular levels of cyclic adenosine monophosphate (cAMP) [cAMP] i 7,9,10 and protein kinase A activation. 11,12 Phosphorylation and opening of a cAMP-dependent Cl Ϫ channel, the cystic fibrosis transmembrane conductance regulator (CFTR), 13 causes Cl Ϫ efflux to the ductular lumen. This appears to stimulate an apical Na ϩ -independent Cl Ϫ /HCO 3 Ϫ anion exchange (AE), 14 with HCO 3 Ϫ efflux and Cl Ϫ influx, that is facilitated by the outside to inside transmembrane gradient of Cl Ϫ at relatively high intracellular HCO 3 Ϫ concentration. [10][11][12]15,16 Several bicarbonate transporters, most of them encoded by the SLC4 and SLC26 gene families, 17 have been described to exert AE activity. A decade ago, we localized one of those polypeptides, the SLC4A2 or AE2, 18 to the apical membrane in...

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Section: Discussionmentioning

confidence: 99%

Bicarbonate-rich choleresis induced by secretin in normal rat is taurocholate-dependent and involves AE2 anion exchanger

et al. 2006

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“…The sympathetic nervous system promotes hepatic glucose production by activating glycogenolysis in fed states and accelerating gluconeogenesis in fasted states. Hepatic glucose metabolism is under the direct control of hepatic autonomic innervation [13,14,21]. Electrical stimulation of the peripheral end of the left splanchnic nerve of rabbits produces rapid increases in the activities of liver enzymes.…”

Section: Sympathetic Effects On Glucose and Fat Metabolismmentioning

confidence: 99%

“…In perfused rat liver, activation of the sympathetic liver nerves causes increases in glucose release and the activity of glycogen phosphorylase and a decrease in the activity of glycogen synthase. In addition, sympathetic stimulation decreases the flow and elicits an intrahepatic redistribution as well as a mobilisation of blood by the closing of sinusoids [13]. Activation of parasympathetic nerves enhances glucose utilisation and causes re-opening of previously closed sinusoids.…”

Section: Sympathetic Effects On Glucose and Fat Metabolismmentioning

confidence: 99%

“…Activation of parasympathetic nerves enhances glucose utilisation and causes re-opening of previously closed sinusoids. The actions of hepatic nerves are modulated by hormones including glucagon, insulin, epinephrine and norepinehrine [13]. In humans, subjects who have had liver transplants have normal postabsorptive glucose metabolism and a glucose and insulin challenge elicit a normal response at both hepatic and peripheral sites.…”

Section: Sympathetic Effects On Glucose and Fat Metabolismmentioning

confidence: 99%

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New insights into sympathetic regulation of glucose and fat metabolism

2000

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Since the observation by Claude Bernard in the 1850 s that puncture of the floor of the fourth ventricle in dogs results in the appearance of transient glucosuria, the central nervous system (CNS) has been implicated in the control of certain metabolic processes of energy homeostasis mainly through neuroendocrine systems. After its recent discovery, leptin, an adipocyte hormone, has been proposed to signal the CNS to modulate autonomic outflow and food intake, leading to alterations of energy metabolism [1,2]. Leptin has been suggested to increase sympathetic outflow and disturbances of leptin signalling lead to Diabetologia (2000) 43: 533±549 ReviewsNew insights into sympathetic regulation of glucose and fat metabolism AbstractThe autonomic nervous system modulates glucose and fat metabolism through both direct neural effects and hormonal effects. This review presents recent concepts on the sympathetic regulation of glucose and fat metabolism. Focally released norepinephrine from sympathetic nerves is likely to increase glucose uptake in skeletal muscle and adipose tissues independent of insulin but norepinephrine does not contribute so much as epinephrine to hepatic glucose production. Epinephrine increases hepatic glucose production and inhibits insulin secretion and the glucose uptake by tissues that is induced by insulin. Additionally, catecholamines can increase thermogenesis and lipolysis, leading to increased energy expenditure and decreased fat stores. It is likely that b-(b3)-adrenergic receptors mediate these responses. Alterations of central neurotransmission and environmental factors can change the relative contribution of sympathetic outflow to the pancreas, liver, adrenal medulla and adipose tissues, leading to the modulation of glucose and fat metabolism. Recent studies have proposed that leptin, an adipocyte hormone, affects the central nervous system to increase sympathetic outflow independent of feeding. The effects of leptin on glucose and fat metabolism could be in part mediated by the sympathetic nervous system. Studies using mice with a genetic disruption of serotonin 5-HT2 c receptor indicate that central neural mechanisms in the regulation of sympathetic outflow and satiety could be dissociated. Abnormalities of sympathetic effects, including disturbances of leptin and b3-adrenergic receptor signalling, are likely to cause obesity and impaired glucose tolerance in rodents and humans. These findings indicate that dysfunction of the sympathetic nervous system could predispose to obesity and Type II (non-insulin-dependent) diabetes mellitus. [Diabetologia (2000) 43: 533±549]

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“…Various physiological functions of mesenteric organs are closely controlled by the sympathetic innervation (Gardemann et al, 1992;SjoÈ vall et al, 1987). Because of the relative inaccessibility of the mesenteric organs to physiological investigation, the contribution to total body catecholamine spillover and turnover was realized only recently.…”

Section: Introductionmentioning

confidence: 99%

Catecholamine transport by the organic cation transporter type 1 (OCT1)

Breidert

Spitzenberger

Gründemann

et al. 1998

British J Pharmacology

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Liver and kidney extract adrenaline and noradrenaline from the circulation by a mechanism which does not seem to be one of the classical catecholamine transporters. The hypothesis that OCT1 is involved–the organic cation transporter type 1 which exists in rat kidney and liver–was tested. Based on human embryonic kidney cells (293), we constructed a cell line which stably expresses OCT1r (293OCT1r cells). Transfection with OCT1 resulted in a transport activity not only for prototypical known substrates of OCT1 such as 3H‐1‐methyl‐4‐phenylpyridinium and 14C‐tetraethylammonium but also for the catecholamines 3H‐adrenaline, 3H‐noradrenaline (3H‐NA) and 3H‐dopamine (3H‐DA), the indoleamine 3H‐5‐hydroxytryptamine (3H‐5HT) as well as the indirect sympathomimetic 14C‐tyramine. For 3H‐DA, 3H‐5HT and 3H‐NA, at non‐saturating concentrations, the rate constants for inwardly directed substrate flux (kin) were 6.9±0.8, 3.1±0.2, and 1.2±0.1 μl min−1 mg protein−1. In wild type cells (293WT) the corresponding kin's were considerably lower, being 0.94±0.40, 0.47±0.08 and 0.23±0.05 μl min−1 mg protein−1 (n=12). The indirectly determined half‐saturating concentrations of DA, 5HT, and NA were 1.1 (95% c.i.: 0.8, 1.4), 0.65 (0.49, 0.86), and 2.8 (2.1, 3.7) mmol l−1 (n=3). Specific 3H‐DA uptake in 293OCT1r cells was resistant to cocaine (1 μmol l−1), 3H‐5HT uptake was resistant to citalopram (300 nmol l−1) and 3H‐NA uptake was resistant to desipramine (100 nmoll−1), corticosterone (1 μmol l−1), and reserpine (10 nmol l−1) which rules out the involvement of classical transporters for biogenic amines. The findings demonstrate that OCT1 efficiently transports catecholamines and other biogenic amines and support the hypothesis that OCT1 is responsible for hepatic and renal inactivation of circulating catecholamines. British Journal of Pharmacology (1998) 125, 218–224; doi:10.1038/sj.bjp.0702065

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Nervous control of liver metabolism and hemodynamics

Cited by 20 publications

References 108 publications

Bicarbonate-rich choleresis induced by secretin in normal rat is taurocholate-dependent and involves AE2 anion exchanger

Bicarbonate-rich choleresis induced by secretin in normal rat is taurocholate-dependent and involves AE2 anion exchanger

New insights into sympathetic regulation of glucose and fat metabolism

Catecholamine transport by the organic cation transporter type 1 (OCT1)

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