Histamine induces intracellular Ca2+ oscillations and nitric oxide release in endothelial cells from brain microvascular circulation. 2020

Roberto Berra-Romani, and Pawan Faris, and Giorgia Pellavio, and Matteo Orgiu, and Sharon Negri, and Greta Forcaia, and Verónica Var-Gaz-Guadarrama, and Mario Garcia-Carrasco, and Laura Botta, and Giulio Sancini, and Umberto Laforenza, and Francesco Moccia
Department of Biomedicine, Biomedicine School, Benemerita Universidad Autonoma de Puebla, Puebla, Mexico.

The neuromodulator histamine is able to vasorelax in human cerebral, meningeal and temporal arteries via endothelial histamine 1 receptors (H1 Rs) which result in the downstream production of nitric oxide (NO), the most powerful vasodilator transmitter in the brain. Although endothelial Ca 2+ signals drive histamine-induced NO release throughout the peripheral circulation, the mechanism by which histamine evokes NO production in human cerebrovascular endothelial cells is still unknown. Herein, we exploited the human cerebral microvascular endothelial cell line, hCMEC/D3, to assess the role of intracellular Ca 2+ signaling in histamine-induced NO release. To achieve this goal, hCMEC/D3 cells were loaded with the Ca 2+ - and NO-sensitive dyes, Fura-2/AM and DAF-FM/AM, respectively. Histamine elicited repetitive oscillations in intracellular Ca 2+ concentration in hCMEC/D3 cells throughout a concentration range spanning from 1 pM up to 300 μM. The oscillatory Ca 2+ response was suppressed by the inhibition of H 1 Rs with pyrilamine, whereas H 1 R was abundantly expressed at the protein level. We further found that histamine-induced intracellular Ca 2+ oscillations were initiated by endogenous Ca 2+ mobilization through inositol-1,4,5-trisphosphate- and nicotinic acid dinucleotide phosphate-sensitive channels and maintained over time by store-operated Ca 2+ entry. In addition, histamine evoked robust NO release that was prevented by interfering with the accompanying intracellular Ca 2+ oscillations, thereby confirming that the endothelial NO synthase is recruited by Ca 2+ spikes also in hCMEC/D3 cells. These data provide the first evidence that histamine evokes NO production from human cerebrovascular endothelial cells through intracellular Ca 2+ oscillations, thereby shedding novel light on the mechanisms by which this neuromodulator controls cerebral blood flow.

UI MeSH Term Description Entries
D009249 NADP Nicotinamide adenine dinucleotide phosphate. A coenzyme composed of ribosylnicotinamide 5'-phosphate (NMN) coupled by pyrophosphate linkage to the 5'-phosphate adenosine 2',5'-bisphosphate. It serves as an electron carrier in a number of reactions, being alternately oxidized (NADP+) and reduced (NADPH). (Dorland, 27th ed) Coenzyme II,Nicotinamide-Adenine Dinucleotide Phosphate,Triphosphopyridine Nucleotide,NADPH,Dinucleotide Phosphate, Nicotinamide-Adenine,Nicotinamide Adenine Dinucleotide Phosphate,Nucleotide, Triphosphopyridine,Phosphate, Nicotinamide-Adenine Dinucleotide
D009569 Nitric Oxide A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP. Endogenous Nitrate Vasodilator,Mononitrogen Monoxide,Nitric Oxide, Endothelium-Derived,Nitrogen Monoxide,Endothelium-Derived Nitric Oxide,Monoxide, Mononitrogen,Monoxide, Nitrogen,Nitrate Vasodilator, Endogenous,Nitric Oxide, Endothelium Derived,Oxide, Nitric,Vasodilator, Endogenous Nitrate
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D006632 Histamine An amine derived by enzymatic decarboxylation of HISTIDINE. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. Ceplene,Histamine Dihydrochloride,Histamine Hydrochloride,Peremin
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D017442 Histamine Agonists Drugs that bind to and activate histamine receptors. Although they have been suggested for a variety of clinical applications histamine agonists have so far been more widely used in research than therapeutically. Histamine H1 Agonists,Histamine H2 Agonists,Histamine H3 Agonists,H1 Agonist,H1 Agonists,H2 Agonist,H2 Agonists,H3 Agonist,H3 Agonists,Histamine Agonist,Histamine H1 Agonist,Histamine H1 Receptor Agonist,Histamine H1 Receptor Agonists,Histamine H2 Agonist,Histamine H2 Receptor Agonist,Histamine H2 Receptor Agonists,Histamine H3 Agonist,Histamine H3 Receptor Agonists,Histaminergic Agonist,Histaminergic Agonists,Agonist, H1,Agonist, H2,Agonist, H3,Agonist, Histamine,Agonist, Histamine H1,Agonist, Histamine H2,Agonist, Histamine H3,Agonist, Histaminergic,Agonists, H1,Agonists, H2,Agonists, H3,Agonists, Histamine,Agonists, Histamine H1,Agonists, Histamine H2,Agonists, Histamine H3,Agonists, Histaminergic,H1 Agonist, Histamine,H1 Agonists, Histamine,H2 Agonist, Histamine,H2 Agonists, Histamine,H3 Agonist, Histamine,H3 Agonists, Histamine
D042783 Endothelial Cells Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer. Capillary Endothelial Cells,Lymphatic Endothelial Cells,Vascular Endothelial Cells,Capillary Endothelial Cell,Cell, Capillary Endothelial,Cell, Endothelial,Cell, Lymphatic Endothelial,Cell, Vascular Endothelial,Cells, Capillary Endothelial,Cells, Endothelial,Cells, Lymphatic Endothelial,Cells, Vascular Endothelial,Endothelial Cell,Endothelial Cell, Capillary,Endothelial Cell, Lymphatic,Endothelial Cell, Vascular,Endothelial Cells, Capillary,Endothelial Cells, Lymphatic,Endothelial Cells, Vascular,Lymphatic Endothelial Cell,Vascular Endothelial Cell
D053496 Inositol 1,4,5-Trisphosphate Receptors Intracellular receptors that bind to INOSITOL 1,4,5-TRISPHOSPHATE and play an important role in its intracellular signaling. Inositol 1,4,5-trisphosphate receptors are calcium channels that release CALCIUM in response to increased levels of inositol 1,4,5-trisphosphate in the CYTOPLASM. Inositol 1,4,5-Triphosphate Receptor,Inositol 1,4,5-Triphosphate Receptors,Inositol 1,4,5-Trisphosphate Receptor,1,4,5-INTP Receptor,INSP3 Receptor,INSP3 Receptor Type 1,INSP3 Receptor Type 2,INSP3 Receptor Type 3,IP3 Receptor,Inositol 1,4,5-trisphosphate Receptor Subtype 3,Inositol 1,4,5-trisphosphate Receptor Type 1,Inositol 1,4,5-trisphosphate Receptor Type 2,Inositol 1,4,5-trisphosphate Receptor Type 3,Inositol Triphosphate Receptor,Inositol-1,4,5-Triphosphate Receptor,Receptor, Inositol-1,4,5-triphosphate,Type 1 Inositol 1,4,5-trisphosphate Receptor,Type 3 Inositol 1,4,5-trisphosphate Receptor,Receptor, INSP3,Receptor, IP3,Receptor, Inositol Triphosphate,Triphosphate Receptor, Inositol

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