title: Desipramine inhibits histamine H1 receptor-induced Ca2+ signaling in rat hypothalamic cells.
abstract: The hypothalamus in the brain is the main center for appetite control and integrates signals from adipose tissue and the gastrointestinal tract. Antidepressants are known to modulate the activities of hypothalamic neurons and affect food intake, but the cellular and molecular mechanisms by which antidepressants modulate hypothalamic function remain unclear. Here we have investigated how hypothalamic neurons respond to treatment with antidepressants, including desipramine and sibutramine. In primary cultured rat hypothalamic cells, desipramine markedly suppressed the elevation of intracellular Ca(2+) evoked by histamine H1 receptor activation. Desipramine also inhibited the histamine-induced Ca(2+) increase and the expression of corticotrophin-releasing hormone in hypothalamic GT1-1 cells. The effect of desipramine was not affected by pretreatment with prazosin or propranolol, excluding catecholamine reuptake activity of desipramine as an underlying mechanism. Sibutramine which is also an antidepressant but decreases food intake, had little effect on the histamine-induced Ca(2+) increase or AMP-activated protein kinase activity. Our results reveal that desipramine and sibutramine have different effects on histamine H1 receptor signaling in hypothalamic cells and suggest that distinct regulation of hypothalamic histamine signaling might underlie the differential regulation of food intake between antidepressants.
authors.affiliation: Department of Physiology, Dental Research Institute, Seoul National University School of Dentistry, Seoul Republic of Korea.
authors.forename: Ji-Ah
authors.initials: JA
authors.lastname: Kang
authors.forename: Keimin
authors.initials: K
authors.lastname: Lee
authors.forename: Kwang Min
authors.initials: KM
authors.lastname: Lee
authors.forename: Sukhee
authors.initials: S
authors.lastname: Cho
authors.forename: Jinsoo
authors.initials: J
authors.lastname: Seo
authors.forename: Eun-Mi
authors.initials: EM
authors.lastname: Hur
authors.forename: Chul-Seung
authors.initials: CS
authors.lastname: Park
authors.forename: Ja-Hyun
authors.initials: JH
authors.lastname: Baik
authors.forename: Se-Young
authors.initials: SY
authors.lastname: Choi
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D003503:Cyclobutanes / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011969:Receptors, Histamine H1 / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D003503:Cyclobutanes; D011969:Receptors, Histamine H1; D006632:Histamine; D003346:Corticotropin-Releasing Hormone; D055372:AMP-Activated Protein Kinases; D002118:Calcium; D003891:Desipramine; C058254:sibutramine