Desipramine Inhibits Histamine H1 Receptor-Induced Ca2+ Signaling in Rat Hypothalamic Cells

Kang, Ji Ah; Lee, Keimin; Lee, Kwang Min; Cho, Sukhee; Seo, Jinsoo; Hur, Eun Mi; Park, Chul–Seung; Baik, Ja Hyun; Choi, Se‐Young

doi:10.1371/journal.pone.0036185

Cited by 5 publications

(4 citation statements)

References 37 publications

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“…Hypothalamic AMPK is also involved in feeding regulation and food intake by regulating the AMPK-ACC-Malonyl-CoA-CPT1 axis (ACC: acetyl-CoA carboxylase; CPT1: carnitine palmitoyltransferase 1) [91][92][93][94]. A study using the CT1-1 cell line reported that the protein level of phosphor-AMPK (pAMPK) is activated by the H 1 R antagonist chlorpheniramine, while it is blocked by histamine [95].…”

Section: The Role Of Hypothalamic H 1 R-ampk Signalling In Sga-inducementioning

confidence: 99%

Ameliorating antipsychotic-induced weight gain by betahistine: Mechanisms and clinical implications

Lian

Huang

Pai

et al. 2016

Pharmacological Research

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Second generation antipsychotic drugs (SGAs) cause substantial body weight gain/obesity and other metabolic side-effects such as dyslipidaemia. Their antagonistic affinity to the histaminergic H1 receptor (H1R) has been identified as one of the main contributors to weight gain/obesity side-effects. The effects and mechanisms of betahistine (a histaminergic H1R agonist and H3 receptor antagonist) have been investigated for ameliorating SGA-induced weight gain/obesity in both animal models and clinical trials. It has been demonstrated that co-treatment with betahistine is effective in reducing weight gain, associated with olanzapine in drug-naïve patients with schizophrenia, as well as in the animal models of both drug-naïve rats and rats with chronic, repeated exposure to olanzapine. Betahistine co-treatment can reduce food intake and increase the effect of thermogenesis in brown adipose tissue by modulating hypothalamic H1R-NPY-AMPKα (NPY: neuropeptide Y; AMPKα: AMP-activated protein kinase α) pathways, and ameliorate olanzapineinduced dyslipidaemia through modulation of AMPKα-SREBP-1-PPARα-dependent pathways (SREBP-1: Sterol regulatory element binding protein 1; PPARα: Peroxisome proliferator-activated receptor-α) in the liver. Although reduced locomotor activity was observed from antipsychotic treatment in rats, betahistine did not affect locomotor activity. Importantly, betahistine co-treatment did not influence the effects of antipsychotics on serotonergic receptors in the key brain regions for antipsychotic therapeutic efficacy. However, betahistine co-treatment reverses the upregulated dopamine D2 binding caused by chronic olanzapine administration, which may be beneficial in reducing D2 supersensitivity often observed in chronic antipsychotic treatment. Therefore, these results provide solid evidence supporting further clinical trials in treating antipsychotics-induced weight gain using betahistine in patients with schizophrenia and other mental disorders.

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Section: The Role Of Hypothalamic H 1 R-ampk Signalling In Sga-inducementioning

confidence: 99%

Ameliorating antipsychotic-induced weight gain by betahistine: Mechanisms and clinical implications

Lian

Huang

Pai

et al. 2016

Pharmacological Research

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“…Recently, a study on the hypothalamic GT1-1 cell line also found similar results; the H1 receptor antagonist, chlorpheniramine, increased the protein level of phosphor-AMPK (pAMPK: activated AMPK), which could be blocked by histamine. [73] A range of evidence has demonstrated that activation of hypothalamic AMPK increases food intake and body weight, while inhibition of hypothalamic AMPK decreases feeding and body…”

Section: The Role Of Histamine and Histamine H1 Receptors In Second-gmentioning

confidence: 99%

The Role of Hypothalamic H1 Receptor Antagonism in Antipsychotic-Induced Weight Gain

Deng

Huang

2013

CNS Drugs

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Treatment with second generation antipsychotics (SGAs), notably olanzapine and clozapine, causes severe obesity side effects. Antagonism of histamine H1 receptors has been identified as a main cause of SGAinduced obesity, but the molecular mechanisms associated with this antagonism in different stages of SGAinduced weight gain remain unclear. This review aims to explore the potential role of hypothalamic histamine H1 receptors in different stages of SGA-induced weight gain/obesity and the molecular pathways related to SGA-induced antagonism of these receptors. Initial data have demonstrated the importance of hypothalamic H1 receptors in both short-and long-term SGA-induced obesity. Blocking hypothalamic H1 receptors by SGAs activates AMP-activated protein kinase (AMPK), a well-known feeding regulator. During short-term treatment, hypothalamic H1 receptor antagonism by SGAs may activate the AMPK-carnitine palmitoyltransferase 1 signaling to rapidly increase caloric intake and result in weight gain. During long-term SGA treatment, hypothalamic H1 receptor antagonism can reduce thermogenesis, possibly by inhibiting the sympathetic outflows to the brainstem rostral raphe pallidus and rostral ventrolateral medulla, therefore decreasing brown adipose tissue thermogenesis. Additionally, blocking of hypothalamic H1 receptors by SGAs may also contribute to fat accumulation by decreasing lipolysis but increasing lipogenesis in white adipose tissue. In summary, antagonism of hypothalamic H1 receptors by SGAs may time-dependently affect the hypothalamus-brainstem circuits to cause weight gain by stimulating appetite and fat accumulation but reducing energy expenditure. The H1 receptor and its downstream signaling molecules could be valuable targets for the design of new compounds for treating SGA-induced weight gain/obesity.

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“…We observed an increase in the level of phospho AMPK and plasma adiponectin. A study by Kang et al [40] has shown similar results for AMPK and an increase in serum adiponectin with sibutramine administration has been reported [41,42]. No previous studies have reported the effect of sibutramine on CPT-1 activity.…”

Section: Discussionmentioning

confidence: 52%

Effect of Short Term Sibutramine Supplementation on Appetite Suppression and Related Metabolic Responses

Singh

2012

J. Pharm. Nutr. Sci.

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The appetite suppressing property of Sibutramine is well reported. The present study was undertaken to investigate the appetite regulatory mechanism and associated metabolic changes induced in male Sprague Dawley rats by its short term supplementation. The effect of the drug on the regulatory hormones and biochemical variables was studied at an oral dose of 10 mg/kg body weight. There was a decrease in food intake of rats by 35.5% in comparison to their basal food intake as well as untreated controls. There was an increase in plasma levels of adiponectin, serotonin and a decrease in IGF-1 and corticosterone in the treated animals. The circulating levels of ghrelin marginally decreased with a corresponding increase in leptin and CCK in case of treated rats. These may be responsible for the anorectic effect of the drug.

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Desipramine Inhibits Histamine H1 Receptor-Induced Ca2+ Signaling in Rat Hypothalamic Cells

Cited by 5 publications

References 37 publications

Ameliorating antipsychotic-induced weight gain by betahistine: Mechanisms and clinical implications

Ameliorating antipsychotic-induced weight gain by betahistine: Mechanisms and clinical implications

The Role of Hypothalamic H1 Receptor Antagonism in Antipsychotic-Induced Weight Gain

Effect of Short Term Sibutramine Supplementation on Appetite Suppression and Related Metabolic Responses

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