Adrenergic agents as possible regulators of liver regeneration

Morley, Colin G.D.; Royse, Vicki L.

doi:10.1016/0020-711x(81)90001-x

Cited by 46 publications

(19 citation statements)

References 30 publications

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“…Furthermore, our data suggest that these fluctuations in cAMP levels result from variations in the rate ofsynthesis of cAMP by AC, since changes in cAMP concentration correlate well with changes in the activity of this enzyme after PH. Others have noted that hepatic sensitivity to a number of discrete beta-adrenergic agents and glucagon is enhanced after PH (1,23,24). Plasma levels ofcatecholamines, glucagon, and insulin increase post-PH (1,(23)(24)(25)(26).…”

Section: Discussionmentioning

confidence: 99%

“…Others have noted that hepatic sensitivity to a number of discrete beta-adrenergic agents and glucagon is enhanced after PH (1,23,24). Plasma levels ofcatecholamines, glucagon, and insulin increase post-PH (1,(23)(24)(25)(26). Gradual changes in the kinetics of glucagon and alpha-and beta-adrenergic receptors after PH have been reported (24)(25)(26).…”

Section: Discussionmentioning

confidence: 99%

“…Gradual changes in the kinetics of glucagon and alpha-and beta-adrenergic receptors after PH have been reported (24)(25)(26). However, the maximal increases in these receptors occur relatively late in the prereplicative period (24)(25)(26) (1,23,24) that the regenerating liver exhibits a generalized increase in sensitivity to various ligands that induce cAMP synthesis.…”

Section: Discussionmentioning

confidence: 99%

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Differential expression of guanine nucleotide-binding proteins enhances cAMP synthesis in regenerating rat liver.

et al. 1992

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Events leading to cAMP accumulation after partial hepatectomy (PH) and effects ofcAMP on hormonal induction of DNA synthesis in hepatocytes were characterized. Hepatic cAMP peaked biphasically post-PH and paralleled changes in adenylyl cyclase activity. Fluctuations in cyclase activity were not explained by variations in glucagon receptor kinetics, but reflected altered G-protein expression. Membrane levels of the stimulatory G-protein, Gs alpha, increased early after PH and were sustained. Levels of the inhibitory G-protein, Gi2 alpha, increased more slowly, peaked later, and quickly fell. Levels of both G-proteins correlated poorly with levels of their mRNAs, suggesting posttranscriptional factors modify their membrane concentrations. When growth factor-induced DNA synthesis was compared in hepatocyte cultures grown with or without agents that increase intracellular cAMP, DNA synthesis was inhibited by sustained high levels of cAMP but was enhanced when high cAMP levels fell. In both regenerating liver and hepatocyte cultures, the expression of a "differentiated" hepatocyte gene, phosphoenolpyruvate carboxykinase, correlated with elevated cAMP levels. These data suggest that the differential expression of G-proteins integrates signals initiated by several growth factors so that the accumulation of cAMP is tightly regulated post-PH. The ensuing variations in cAMP levels modulate both growth and differentiated functions during liver regeneration. (J. Clin. Invest. 1992Invest. . 89:1706Invest. -1712

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Differential expression of guanine nucleotide-binding proteins enhances cAMP synthesis in regenerating rat liver.

et al. 1992

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“…Moreover, Kato and Shimazu [37]reported that bilateral major splanchnicectomy at the subdiaphragmatic level produced no effect on liver regeneration. However, it has been suggested that adrenergic agents regulate liver regeneration [50]. Cruise et al [51]also reported that noradrenaline stimulated DNA synthesis by cultured rat hepatocytes through α 1 -adrenergic receptors.…”

Section: Autonomic Nervous System and Liver Regenerationmentioning

confidence: 99%

The Role of the Autonomic Nervous System in Liver Regeneration and Apoptosis – Recent Developments

Kiba

2002

Digestion

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Hepatocytes have a great replicative capacity and are capable of repopulating the liver. Previous studies have suggested that the autonomic nervous system regulates liver regeneration and apoptosis. Moreover, the central nervous system modulates them through the autonomic nervous system. The lateral hypothalamus (LH) area and the ventromedial hypothalamus (VMH) nucleus have been studied for their role in the integration of neurohumoral information. The LH is part of the parasympathetic system, while the VMH belongs to the sympathetic system. Lesions of the LH reportedly induced an increase in sympathetic nerve activity, while those in the VMH produced facilitation of vagus nerve activity. Moreover, VMH or LH lesions facilitate hepatic regeneration after partial hepatectomy. Furthermore, the hypothalamus mediates hepatic apoptosis through the autonomic nervous system. Although further studies are needed to define the role clearly, the autonomic nervous system is one of the important factors that regulate liver regeneration and apoptosis.

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“…9 The hepatic sympathetic nervous system has been implicated to be important in DNA synthesis during liver regeneration. 10, 11 Cruise et al 12 reported that norepinephrine stimulated DNA synthesis in cultured rat hepatocytes through the ␣ 1 -adrenergic receptor. Serotonin has been shown to be mitogenic in many non-neuronal cells, exerting its effect by its different receptor-mediated second messenger pathways.…”

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Induction of DNA synthesis in primary cultures of rat hepatocytes by serotonin: Possible involvement of serotonin S2 receptor

Balasubramanian¹,

Paulose²

1998

Hepatology

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The involvement of serotonin and its receptor subtype in the induction of hepatocyte DNA synthesis was investigated in primary cultures of adult rat hepatocytes. Serotonin caused a dose-dependent increase in DNA synthesis in primary cultures of rat hepatocytes in the presence of epidermal growth factor (EGF) and insulin, as measured by The adult mammalian hepatocytes are highly differentiated, nonproliferating cells that can be induced to divide after partial hepatectomy. Liver regeneration after partial hepatectomy is a useful model to study the mechanisms involved in the control of cell growth and division. 1 The re-entry of hepatocytes into the cell cycle is characterized by coordinated waves of DNA synthesis, and cell division is terminated by intrinsic control mechanisms when the original cellular mass has been restored. 2 The hepatic regenerative response may be regulated by hormones such as insulin and thyroid hormones, [3][4][5][6] and by neurotransmitters such as norepinephrine. 7,8 Adult rat hepatocytes can be induced to enter into DNA synthesis and mitosis in primary culture. Liver regeneration studies with replicating hepatocytes in culture can be used to investigate the trophic factors that control the growth of normal and neoplastic hepatocytes. 9 The hepatic sympathetic nervous system has been implicated to be important in DNA synthesis during liver regeneration. 10,11 Cruise et al. 12 reported that norepinephrine stimulated DNA synthesis in cultured rat hepatocytes through the ␣ 1 -adrenergic receptor. Serotonin has been shown to be mitogenic in many non-neuronal cells, exerting its effect by its different receptor-mediated second messenger pathways. The S 2 receptor subtype of serotonin has been shown to mediate cell growth in fibroblasts. 13 The serotonin S 2 receptor has been cloned in the human liver and has been shown to have a high degree of homology with the S 2 receptors of rat and mouse liver. 14 The S 2 receptors of serotonin are coupled to phospho-inositide turnover and diacylglycerol formation, which activates protein kinase C (PKC), an important second messenger for cell division. 15 Serotonin S 2 receptor-mediated activation of PKC has been shown to result in the phosphorylation of a 40-kd substrate protein of PKC in human platelets. 16 In the present study, the effect of serotonin and the serotonergic S 2 receptor antagonists, ketanserin and spiperone, in induction of DNA synthesis in primary cultures of adult rat hepatocytes was investigated. The changes in the serotonin S 2 receptors and S 2 receptor-mediated membrane protein phosphorylation were also studied in the regenerating rat liver after partial hepatectomy. 1 MATERIALS AND METHODSAnimals. Adult male Sprague-Dawley rats weighing 200 to 300 g were used for all experiments. They were fed lab chow and water ad libitum, and maintained on a 12-hour light/dark cycle. Isolation and Culture of Hepatocytes. Hepatocytes were isolated from male Sprague-Dawley rats (range, 200-300 g) by collagenase perfusion, filtration, and low-spee...

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Adrenergic agents as possible regulators of liver regeneration

Cited by 46 publications

References 30 publications

Differential expression of guanine nucleotide-binding proteins enhances cAMP synthesis in regenerating rat liver.

Differential expression of guanine nucleotide-binding proteins enhances cAMP synthesis in regenerating rat liver.

The Role of the Autonomic Nervous System in Liver Regeneration and Apoptosis – Recent Developments

Induction of DNA synthesis in primary cultures of rat hepatocytes by serotonin: Possible involvement of serotonin S2 receptor

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