Discovery of a Novel Member of the Histamine Receptor Family

Nguyen, Tuan; Shapiro, D. A.; George, Susan R.; Setola, Vincent; Lee, Dennis K.; Cheng, Regina; Rauser, Laura; Lee, Samuel P.; Lynch, Kevin R.; Roth, Bryan L.; O’Dowd, Brian F.

doi:10.1124/mol.59.3.427

Cited by 333 publications

(270 citation statements)

References 18 publications

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“…Similarly, by altering the lipid environment, apoE deficiency may reduce the total number of H 3 receptor binding sites available for ligand binding in the amygdala, hippocampus, and cortex. Recently, the H 4 receptor was cloned and characterized (Nakamura et al, 2000;Oda et al, 2000;Liu et al, 2001;Morse et al, 2001;Nguyen et al, 2001;Zhu et al, 2001). To determine whether H 4 signaling was involved in the observed effects on object recognition, we tested mice treated with the H 4 receptor agonist and H 3 receptor antagonist clobenpropit (Oda et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…Wild-type and Apoe -/-mice (3-5 months old) received saline, thioperamide, or clobenpropit during the training (day 4) and retention (day 5) sessions. The recently cloned H 4 receptor (Oda et al, 2000;Liu et al, 2001;Morse et al, 2001;Nguyen et al, 2001;Zhu et al, 2001) was found to have an affinity for H 3 -specific ligands. To rule out the possible contribution of the H 4 receptor to the effects of thioperamide, we also treated wild-type and Apoe -/-mice with clobenpropit, None of the differences between wild-type and Apoe -/-mice were significant.…”

Section: Effects Of H 3 Ligands On Novel Object Recognition In Wild-tmentioning

confidence: 99%

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Role of H3-Receptor-Mediated Signaling in Anxiety and Cognition in Wild-Type and Apoe–/– Mice

Bongers

Leurs

Robertson

et al. 2003

Neuropsychopharmacol

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Increasing evidence supports a role for histamine as a neurotransmitter and neuromodulator in emotion and cognition. The H 3 receptor was first characterized as an autoreceptor that modulates histamine release and synthesis via negative feedback. Mice deficient in apoE (Apoe -/-) have been used to define the role of apoE in brain function. In the present study, we investigated the possible role of histamine H 3 -receptor-mediated signaling in anxiety and cognition in mice Apoe -/-and wild-type mice. H 3 antagonists increased measures of anxiety in wild-type, but not Apoe -/-, mice. In contrast, H 3 antagonists similarly impaired object recognition in wild-type and Apoe -/-mice. In Apoe -/-mice, reduced negative feedback via H 3 receptors could contribute to increased signaling of H 1 receptors. Apoe -/-mice showed higher sensitivity to the anxiety-reducing effects of the H 1 receptor antagonist mepyramine than wild-type mice. These effects were dissociated from effects of mepyramine on the HPA axis. Compared to saline controls, mepyramine reduced plasma ACTH and corticosterone levels in wild-type, but not Apoe -/-, mice. These data support a role for apoE in H 3 receptor signaling. H 3 antagonists were proposed as a treatment for cognitive disorders such as Alzheimer's disease, which is associated with increased anxiety and cognitive impairments. As H 3 antagonists increase measures of anxiety and impair object recognition in wild-type mice, the use of H 3 antagonists in cognitive disorders may be counterproductive and should be carefully evaluated.

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Section: Discussionmentioning

confidence: 99%

Section: Effects Of H 3 Ligands On Novel Object Recognition In Wild-tmentioning

confidence: 99%

Role of H3-Receptor-Mediated Signaling in Anxiety and Cognition in Wild-Type and Apoe–/– Mice

Bongers

Leurs

Robertson

et al. 2003

Neuropsychopharmacol

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“…Altered glucose homeostasis and metabolism as well as increased food intake have been proposed as mechanisms responsible for antipsychotic-drug-induced weight gain. Typical and atypical antipsychotic drugs have a complex pharmacology, interacting with a number of serotonergic (eg 5-HT 1A , 5-HT 2A , 5-HT 2C , 5-HT 6 and 5-HT 7 (Roth et al, 1992(Roth et al, , 1994(Roth et al, , 1998, dopaminergic (eg D 2 , D 3 , and D 4 (Seeman and Lee, 1975;Seeman et al, 1997;Van Tol et al, 1991), histaminergic (eg H 1 (Peroutka et al, 1980) and H 4 (Nguyen et al, 2001)), adrenergic, and muscarinic acetylcholine receptors (Bolden et al, 1992;Zeng et al, 1997). In mice, targeted deletion of some of these receptors can have effects on body weight; for example, 5-HT 2C receptor knockout mice are obese (Tecott et al, 1995), whereas m3-muscarinic receptor knockout mice are lean (Yamada et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

H1-Histamine Receptor Affinity Predicts Short-Term Weight Gain for Typical and Atypical Antipsychotic Drugs

Kroeze

Hufeisen

Popadak

et al. 2003

Neuropsychopharmacol

685

488

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As a result of superior efficacy and overall tolerability, atypical antipsychotic drugs have become the treatment of choice for schizophrenia and related disorders, despite their side effects. Weight gain is a common and potentially serious complication of some antipsychotic drug therapy, and may be accompanied by hyperlipidemia, hypertension and hyperglycemia and, in some extreme cases, diabetic ketoacidosis. The molecular mechanism(s) responsible for antipsychotic drug-induced weight gain are unknown, but have been hypothesized to be because of interactions of antipsychotic drugs with several neurotransmitter receptors, including 5-HT 2A and 5-HT 2C serotonin receptors, H 1 -histamine receptors, a 1 -and a 2 -adrenergic receptors, and m3-muscarinic receptors. To determine the receptor(s) likely to be responsible for antipsychotic-drug-induced weight gain, we screened 17 typical and atypical antipsychotic drugs for binding to 12 neurotransmitter receptors. H 1 -histamine receptor affinities for this group of typical and atypical antipsychotic drugs were significantly correlated with weight gain (Spearman r ¼ À0.72; po0.01), as were affinities for a 1A adrenergic (r ¼ À0.54; po0.05), 5-HT 2C (r ¼ À0.49; po0.05) and 5-HT 6 receptors (r ¼ À0.54; po0.05), whereas eight other receptors' affinities were not. A principal components analysis showed that affinities at the H 1 , a 2A , a 2B , 5-HT 2A , 5-HT 2C , and 5-HT 6 receptors were most highly correlated with the first principal component, and affinities for the D 2 , 5-HT 1A , and 5-HT 7 receptors were most highly correlated with the second principal component. A discriminant functions analysis showed that affinities for the H 1 and a 1A receptors were most highly correlated with the discriminant function axis. The discriminant function analysis, as well as the affinity for the H 1 -histamine receptor alone, correctly classified 15 of the 17 drugs into two groups; those that induce weight gain and those that do not. Because centrally acting H 1 -histamine receptor antagonists are known to induce weight gain with chronic use, and because H 1 -histamine receptor affinities are positively correlated with weight gain among typical and atypical antipsychotic drugs, it is recommended that the next generation of atypical antipsychotic drugs be screened to avoid H 1 -histamine receptors.

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“…The histamine effects in the skin associated with urticaria, particularly the wheals and the itch, are mediated through H 1 receptors located on nerves and endothelial cells[11]. A role in urticaria has been proposed also for the H 4 receptors in the generation of pruritus and eosinophil chemotaxis[12]. The histamine receptors exhibit stereochemical differences, which can be recognized by different chemical compounds, referred to as specific receptor agonists.…”

Section: The Role Of Histamine In Ciumentioning

confidence: 99%

Challenges in the Management of Chronic Urticaria

Popov¹

2011

World Allergy Organization Journal

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The term "chronic idiopathic urticaria" denotes a spectrum of conditions with different poorly understood pathogenetic mechanisms in which the release of histamine plays a role. Nonsedating second-generation H1 antihistamines are postulated to be the first line of treatment of chronic idiopathic urticaria by national and international guidelines, but as control is not always achievable with the usually recommended doses, first-generation sedating antihistamines like hydroxyzine and diphenhydramine at high daily doses (200 mg) have been proposed as an alternative before resorting to treatment with systemic corticosteroids and other potentially hazardous agents. Our long time experience and recent research give us grounds to believe that increasing the doses of nonsedating H1 antihistamines up to fourfold improves significantly the chances of successful treatment. Our data suggest that the urticaria-associated discomfort is relieved by higher than conventional doses of levoce-tirizine and desloratadine in about 75% of the patients and that sedation/somnolence does not seem to be a major deterrent. The dose increase also improves the urticaria-specific quality of life. Contrary to the belief that individual patients may benefit from one antihistamine or another, we demonstrate that the drug with better ability to suppress the histamine skin effects in experiments in healthy volunteers (levocetirizine) is also superior in improving the different aspects of control of chronic urticaria (subjective and objective symptoms, quality of life) and that increasing its dose of up to fourfold may even paradoxically reduce the sense of sedation/somnolence in parallel with the relief of urticaria discomfort.

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Discovery of a Novel Member of the Histamine Receptor Family

Cited by 333 publications

References 18 publications

Role of H3-Receptor-Mediated Signaling in Anxiety and Cognition in Wild-Type and Apoe–/– Mice

Role of H3-Receptor-Mediated Signaling in Anxiety and Cognition in Wild-Type and Apoe–/– Mice

H1-Histamine Receptor Affinity Predicts Short-Term Weight Gain for Typical and Atypical Antipsychotic Drugs

Challenges in the Management of Chronic Urticaria

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