@article {1364506,
	title = {Effect of histamine on Ca(2+)-dependent signaling pathways in rat conjunctival goblet cells},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {53},
	number = {11},
	year = {2012},
	month = {2012 Oct 05},
	pages = {6928-38},
	abstract = {PURPOSE: The purpose of this study was to determine the Ca(2+)-dependent cellular signaling pathways used by histamine to stimulate conjunctival goblet cell secretion. METHODS: Cultured rat goblet cells were grown in RPMI 1640. Goblet cell secretion of high molecular weight glycoconjugates was measured by an enzyme-linked lectin assay. Intracellular [Ca(2+)] ([Ca(2+)](i)) was measured by loading cultured cells with the Ca(2+) sensitive dye fura-2. The level of [Ca(2+)](i) was measured using fluorescence microscopy. Extracellular regulated kinase (ERK) 2 was depleted using small interfering RNA (siRNA). RESULTS: Histamine-stimulated conjunctival goblet cell secretion of high molecular weight glycoproteins was blocked by removal of extracellular Ca(2+) and depletion of ERK2 by siRNA. Histamine increase in [Ca(2+)](i) was desensitized by repeated addition of agonist and blocked by a phospholipase C antagonist. Histamine at higher doses increased [Ca(2+)](i) by stimulating influx of extracellular Ca(2+), but at a lower dose released Ca(2+) from intracellular stores. Activation of each histamine receptor subtype (H(1)-H(4)) increased [Ca(2+)](i) and histamine stimulation was blocked by antagonists of each receptor subtype. The H(2) receptor subtype increase in [Ca(2+)](i) was cAMP dependent. CONCLUSIONS: We conclude that histamine activates phospholipase C to release intracellular Ca(2+) that induces the influx of extracellular Ca(2+) and activates ERK1/2 to stimulate conjunctival goblet cell mucous secretion, and that activation of all four histamine receptor subtypes can increase [Ca(2+)](i).},
	keywords = {Animals, Calcium, Calcium Signaling, Cells, Cultured, Conjunctiva, Enzyme Activation, Enzyme-Linked Immunosorbent Assay, Fura-2, Goblet Cells, Histamine, Histamine Agonists, Histamine Antagonists, Male, MAP Kinase Signaling System, Microscopy, Fluorescence, Mucins, Rats, Rats, Sprague-Dawley, Receptors, Histamine, RNA, Small Interfering, Type C Phospholipases},
	issn = {1552-5783},
	doi = {10.1167/iovs.12-10163},
	author = {Li, Dayu and Carozza, Richard B and Shatos, Marie A and Hodges, Robin R and Dartt, Darlene A.}
}
