ArticleProceedings of the National Academy of Sciences of the United States of America1996
Inverse agonism of histamine H2 antagonist accounts for upregulation of spontaneously active histamine H2 receptors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
44 citing papers in PubMed, 245 citations in OpenAlex.
- CXCL12 chemokine dimer signaling modulates acute myelogenous leukemia cell migration through altered receptor internalization.Scientific reports · 2025Article
- Know your molecule: pharmacological characterization of drug candidates to enhance efficacy and reduce late-stage attrition.Nature reviews. Drug discovery · 2024Review
- Drug screening in zebrafish larvae reveals inflammation-related modulators of secondary damage after spinal cord injury in mice.Theranostics · 2023Article
- Development of tolerance to chemokine receptor antagonists: current paradigms and the need for further investigation.Frontiers in immunology · 2023Review
- Revisiting Preclinical Observations of Several Histamine H3 Receptor Antagonists/Inverse Agonists in Cognitive Impairment, Anxiety, Depression, and Sleep-Wake Cycle Disorder.Frontiers in pharmacology · 2022Review
- BRET Analysis of GPCR Dimers in Neurons and Non-Neuronal Cells: Evidence for Inactive, Agonist, and Constitutive Conformations.International journal of molecular sciences · 2021Article
- The Roles of Cardiovascular HFrontiers in pharmacology · 2021Review
- A Dynamic, Split-Luciferase-Based Mini-G Protein Sensor to Functionally Characterize Ligands at All Four Histamine Receptor Subtypes.International journal of molecular sciences · 2020Article
- Histamine, histamine receptors, and neuropathic pain relief.British journal of pharmacology · 2020Review
- Making Sense of Pharmacology: Inverse Agonism and Functional Selectivity.The international journal of neuropsychopharmacology · 2018Review
- Can HBritish journal of clinical pharmacology · 2018Article
- The Role of Histamine and Histamine Receptors in Mast Cell-Mediated Allergy and Inflammation: The Hunt for New Therapeutic Targets.Frontiers in immunology · 2018Review
- mGlu1 receptor mediates homeostatic control of intrinsic excitability through Ih in cerebellar Purkinje cells.Journal of neurophysiology · 2016Article
- Computer modeling of gastric parietal cell: significance of canalicular space, gland lumen, and variable canalicular [K+].American journal of physiology. Gastrointestinal and liver physiology · 2016Article
- Preclinical evaluation of SMM-189, a cannabinoid receptor 2-specific inverse agonist.Pharmacology research & perspectives · 2015Article
- The atypical antipsychotics clozapine and olanzapine promote down-regulation and display functional selectivity at human 5-HT7 receptors.British journal of pharmacology · 2015Article
- International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors.Pharmacological reviews · 2015Review
- How genetic errors in GPCRs affect their function: Possible therapeutic strategies.Genes & diseases · 2015Article
- Physiological implications of biased signaling at histamine H2 receptors.Frontiers in pharmacology · 2015Article
- Involvement of histamine receptors in the atypical antipsychotic profile of clozapine: a reassessment in vitro and in vivo.Psychopharmacology · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Histamine H2 receptors transfected in Chinese hamster ovary (CHO) cells are time- and dose-dependently upregulated upon exposure to the H2 antagonists cimetidine and ranitidine. This effect appears to be H2 receptor-mediated as no change in receptor density was observed after H1 or H3 antagonist treatment or after incubation with the structural analogue of cimetidine, VUF 8299, which has no H2 antagonistic effects. By using transfected CHO cells expressing different densities of wild-type H2 receptors or an uncoupled H2Leu124Ala receptor, the histamine H2 receptor was found to display considerable agonist-independent H2 receptor activity. Cimetidine and ranitidine, which both induce H2 receptor upregulation, actually functioned as inverse agonists in those cell lines displaying spontaneous agonist-independent H2 receptor activity. Burimamide, on the other hand, was shown to act as a neutral antagonist and did as expected not induce H2 receptor upregulation after long-term exposure. The displayed inverse agonism of H2 antagonists appears to be a mechanistic basis for the observed H2 antagonist-induced H2 receptor upregulation in transfected CHO cells. These observations shed new light on the pharmacological classification of the H2 antagonists and may offer a plausible explanation for the observed development of tolerance after prolonged clinical use.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.