title: Effect of caffeine on mucus secretion and agonist-dependent Ca2+ mobilization in human gastric mucus secreting cells.
abstract: Caffeine is known to stimulate gastric acid secretion, but, the effects of caffeine on gastric mucus secretion have not been clarified. To elucidate the action of caffeine on gastric mucin-producing cells and its underlying mechanism, the effects of caffeine on mucus glycoprotein secretion and agonist-induced [Ca2+]i mobilization were examined in human gastric mucin secreting cells (JR-I cells). The measurement of [Ca2+]i using Indo-1 and the whole cell voltage clamp technique were applied. Mucus glycoprotein secretion was assessed by release of [3H]glucosamine. Caffeine by itself failed to increase [Ca2+]i and affect membrane currents, while it dose-dependently inhibited agonist (acetylcholine (ACh) or histamine)-induced [Ca2+]i rise, resulting in inhibiting activation of Ca2+-dependent K+ current (I(K.Ca)) evoked by agonists. The effect of caffeine was reversible, and the half maximal inhibitory concentration was about 0.5 mM. But, caffeine did not suppress [Ca2+]i rise and activation of I(K.Ca) induced by A23187 or inositol trisphosphate (IP3). Theophylline or 3-isobutyl-1-methyl-xanthine (IBMX) did not mimic the effect of caffeine. Caffeine failed to stimulate mucus secretion, while it significantly decreased ACh-induced mucus secretion. These results indicate that caffeine selectively inhibits agonist-mediated [Ca2+]i rise in human gastric epithelial cells, probably through the blockade of receptor-IP3 signaling pathway, which may affect the mucin secretion.
authors.affiliation: Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Hamada
authors.forename: T
authors.initials: T
authors.lastname: Nakajima
authors.forename: Y
authors.initials: Y
authors.lastname: Hata
authors.forename: H
authors.initials: H
authors.lastname: Hazama
authors.forename: K
authors.initials: K
authors.lastname: Iwasawa
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
authors.forename: S
authors.initials: S
authors.lastname: Ota
authors.forename: M
authors.initials: M
authors.lastname: Omata
mesh_terms: D002110:Caffeine / Q000494:pharmacology*; D000001:Calcimycin; D002118:Calcium / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007211:Indoles; D007295:Inositol Phosphates; D009077:Mucins / Q000032:analysis; D009093:Mucus / Q000737:chemistry / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D014407:Tumor Cells, Cultured
chemical_list: D007211:Indoles; D007295:Inositol Phosphates; D009077:Mucins; D000001:Calcimycin; D002110:Caffeine; C048960:indo-1; D002118:Calcium