{"title":"Bombesin stimulates dorsal raphe nucleus serotonergic neurons via a mechanism involving BB1 receptors.","authors":"Eliyahu Dremencov, Daniil Grinchii, Xia Zhang, Zul Merali","doi":"10.4149/gpb_2025007","DOIUrl":null,"url":null,"abstract":"<p><p>The involvement of serotonin (5-HT) in mood and appetite regulation is well established. This neurotransmitter is released from the neurons located in brainstem raphe nuclei. The excitability of the raphe 5-HT neurons, determining 5-HT neurotransmission, is regulated by various biomolecules, among them gastroenteric hormones, such as gastrin-releasing peptide (GRP). We aimed to examine the effects of the GRP homolog bombesin, and antagonist of bombesin BB1 receptor PD 176252, on the excitability of 5-HT neurons in in vivo conditions. In order to achieve its permeability through the blood-brain barrier, bombesin was fused to the cell-membrane transduction domain of the human immunodeficiency virus-type-1 Tat protein. We found that Tat-bombesin complex increased the firing activity of 5-HT neurons; PD 176252 had an opposite effect. GRP might thus regulate 5-HT neurotransmission via a mechanism involving BB1 receptors. BB1 ligands may therefore be used for the treatment of mood and eating disorders.</p>","PeriodicalId":12514,"journal":{"name":"General physiology and biophysics","volume":" ","pages":"253-257"},"PeriodicalIF":1.3000,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"General physiology and biophysics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.4149/gpb_2025007","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/3/21 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
The involvement of serotonin (5-HT) in mood and appetite regulation is well established. This neurotransmitter is released from the neurons located in brainstem raphe nuclei. The excitability of the raphe 5-HT neurons, determining 5-HT neurotransmission, is regulated by various biomolecules, among them gastroenteric hormones, such as gastrin-releasing peptide (GRP). We aimed to examine the effects of the GRP homolog bombesin, and antagonist of bombesin BB1 receptor PD 176252, on the excitability of 5-HT neurons in in vivo conditions. In order to achieve its permeability through the blood-brain barrier, bombesin was fused to the cell-membrane transduction domain of the human immunodeficiency virus-type-1 Tat protein. We found that Tat-bombesin complex increased the firing activity of 5-HT neurons; PD 176252 had an opposite effect. GRP might thus regulate 5-HT neurotransmission via a mechanism involving BB1 receptors. BB1 ligands may therefore be used for the treatment of mood and eating disorders.
期刊介绍：
General Physiology and Biophysics is devoted to the publication of original research papers concerned with general physiology, biophysics and biochemistry at the cellular and molecular level and is published quarterly by the Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences.
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