title: Histamine enhances cytotrophoblast invasion by inducing intracellular calcium transients through the histamine type-1 receptor.
abstract: Blastocyst implantation and placentation require molecular and cellular interactions between the uterine endometrium and blastocyst trophectoderm. Previous studies showed that histamine produced in the mouse uterine luminal epithelium interacts with trophoblast histamine type-2 receptors (H2) to initiate blastocyst implantation. However, it is unknown whether similar histamine activity is operative in humans. Using a human cell line (HTR-8/SVneo) derived from first-trimester cytotrophoblasts that expresses both histamine type-1 receptor (H1) and H2, we found that histamine promotes cytotrophoblast invasiveness specifically through activation of H1. Stimulation of H1 in human cytotrophoblasts by histamine induced intracellular Ca2+ (Ca(2+)i) transients by activating phospholipase C and the inositol trisphosphate pathway. The enhanced invasion induced by histamine was blocked by pretreatment with H1 antagonist or by chelation of Ca(2+)i. These findings suggest possible differences between rodents and humans in histamine signaling to the trophoblast.
authors.affiliation: Department of Anatomy & Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Zitao
authors.initials: Z
authors.lastname: Liu
authors.forename: Brian A
authors.initials: BA
authors.lastname: Kilburn
authors.forename: Richard E
authors.initials: RE
authors.lastname: Leach
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.forename: Bibhash C
authors.initials: BC
authors.lastname: Paria
authors.forename: D Randall
authors.initials: DR
authors.lastname: Armant
mesh_terms: D002118:Calcium / Q000502:physiology*; D020013:Calcium Signaling; D002448:Cell Adhesion; D049109:Cell Proliferation; D002478:Cells, Cultured; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D010064:Embryo Implantation; D006632:Histamine / Q000502:physiology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000502:physiology; D011969:Receptors, Histamine H1 / Q000502:physiology*; D011970:Receptors, Histamine H2 / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D014327:Trophoblasts / Q000166:cytology / Q000502:physiology*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D006634:Histamine H1 Antagonists; D007546:Isoquinolines; D010716:Phosphatidylinositols; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D013449:Sulfonamides; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D006632:Histamine; D010738:Type C Phospholipases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D002118:Calcium