Histamine H1 receptor-induced Ca2+ mobilization and prostaglandin E2 release in human gingival fibroblasts: Possible role of receptor-operated Ca2+ influx

doi:10.1016/0006-2952(96)00417-0

Biochemical Pharmacology

Volume 52, Issue 7, 11 October 1996, Pages 1015-1023

https://doi.org/10.1016/0006-2952(96)00417-0 Get rights and content

Abstract

Stimulation of human gingival fibroblasts with histamine elicited an increase in the intracellular concentration of free calcium ([Ca²⁺]_i) and the formation of inositol 1,4,5-trisphosphate (InsP₃) in a concentration- and time-dependent manner. The histamine-induced increase in [Ca²⁺]_i was attenuated completely by chlorpheniramine, an H₁ antagonist, but not by cimetidine, an H₂ antagonist. The histamine-induced Ca²⁺ response consisted of an initial transient peak response and a subsequent sustained increase. The transient phase can be largely attributed to Ca²⁺ release from intracellular InsP₃-sensitive stores since the increased [Ca²⁺]_i effect of histamine completely disappeared after depletion of intracellular Ca²⁺ stores with thapsigargin in the absence of extracellular Ca²⁺. The sustained phase was due to Ca²⁺ influx which was attenuated in the absence of extracellular Ca²⁺. The Ca²⁺ influx required the continuous binding of histamine to the receptor, since chlorpheniramine attenuated the increase in [Ca²⁺]_i observed when extracellular Ca²⁺ was re-applied to the cells after stimulation with histamine in the absence of extracellular Ca²⁺. Pretreatment with the Ca²⁺ channel blocker SK&F96365 inhibited the Ca₂₊ influx component, suggesting that histamine stimulates Ca²⁺ influx through an h₁ receptor-operated Ca²⁺ channel. Histamine also evoked a concentration- and time-dependent release of prostaglandin E₂ (PGE₂). The histamine-evoked PGE₂ release was reduced markedly by exclusion of extracellular Ca²⁺ or pretreatment with SK&F96365 or an H₁ antagonist. These results indicate that histamine stimulates both the intracellular Ca²⁺ release from InsP₃-sensitive stores and the H₁ receptor-operated Ca²⁺ influx from extracellular sites. The increased [Ca²⁺]_i due to the Ca²⁺ influx causes PGE₂ release in human gingival fibroblasts.

References (37)

T Nakamoto et al.
The role of ascorbic acid deficiency in human gingivitis—A new hypothesis
J Theor Biol
(1984)
DE Smith
The tissue mast cells
EN Unemori et al.
Interleukin-1 and transforming growth factor-α: Synergistic stimulation of metalloproteinases, PGE₂, and proliferation in human fibroblasts
Exp Cell Res
(1994)
UH Lerner et al.
Comparison of human interleukin- 1β and its 163–171 peptide in bone resorption and the immune response
Cytokine
(1991)
K Yokota et al.
Stimulation of prostaglandin E₂ synthesis in cloned osteoblastic cells of mouse (MC3T3-E1) by epidermal growth factor
J Biol Chem
(1986)
A Kishimoto et al.
Activation of calcium and phospholipid-dependent protein kinase by diacylglycerol, its possible relation to phosphatidyli-nositol turnover
J Biol Chem
(1980)
Y Takai et al.
Unsaturated diacylglycerol as a possible messenger of the activation of calcium-activated, phospholipid-dependent protein kinase system
Biochem Biophys Res Commun
(1979)
G Grynkiewicz et al.
A new generation of Ca²⁺ indicators with greatly improved fluorescence properties
J Biol Chem
(1985)
H Takemura et al.
Activation of calcium entry by the tumor promoter thapsi-gargin in parotid acinar cells
J Biol Chem
(1989)
TJ Hallam et al.
Receptor-mediated Ca2⁺ entry: Diversity of function and mechanism
Trends Pharmacol Sci
(1989)

MJ Nissinen et al.

Developmental patterns of histamine-like immunoreactivity in the mouse

J Histochem Cytochem

(1995)

R Nisengard

Immediate hypersensitivity and periodontal disease

J Periodontol

(1974)

CL Johnson et al.

Histamine receptors in human fibroblasts: Inositol phosphates, Ca²⁺, and cell growth

Am J Physiol

(1990)

BC Tilly et al.

Histamine as a growth factor and chemoattractant for human carcinoma and melanoma cells: Action through Ca²⁺-mobilizing H₁ receptors

J Cell Biol

(1990)

A Olsson-Wennstrom et al.

The mechanism of basophil histamine release in patients with periodontal disease

Clin Exp Immunol

(1978)

B Uvnas

Release processes in mast cells and their activation by injury

Ann NY Acad Sci

(1967)

JJ Aloe

Diabetes and periodontal disease. Possible role of vitamin C deficiency: An hypothesis

J Periodontol

(1981)

BU Zachrisson

Mast cells of the human gingiva

J Periodont Res

(1967)

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The fluorescence of fura-2-loaded cells was measured with a CAF-110 spectrofluorometer (Nihon Bunkou, Tokyo, Japan) with excitation at 340 and 380 nm and emission at 500 nm. [ Ca2+]i was calculated from the measurement of the ratio of fluorescence intensities (57, 58). All of the experiments were performed three times with different cell batches.
Bone sialoprotein (BSP), an early marker of osteoblast differentiation, has been implicated in the nucleation of hydroxyapatite during de novo bone formation. Prostaglandin E₂ (PGE₂) has anabolic effects on proliferation and differentiation of osteoblasts via diverse signal transduction systems. Because PGE₂ increases the proportion of functional osteoblasts in fetal rat calvarial cell cultures, we investigated the regulation of BSP, as an osteoblastic marker, by PGE₂. Treatment of rat osteosarcoma UMR 106 cells with 3 μm, 300 nm, and 30 nm PGE₂ increased the steady state levels of BSP mRNA about 2.7-, 2.5-, and 2.4-fold after 12 h. From transient transfection assays, the constructs including the promoter sequence of nucleotides (nt) –116 to +60 (pLUC3) were found to enhance transcriptional activity 3.8- and 2.2-fold treated with 3 μm and 30 nm PGE₂ for 12 h. 2-bp mutations were made in an inverted CCAAT box (between nt –50 and –46), a cAMP response element (CRE; between nt –75 and –68), a fibroblast growth factor 2 response element (FRE; nt –92 to –85), and a pituitary-specific transcription factor-1 motif (between nt –111 and –105) within pLUC3 and pLUC7 constructs. Transcriptional stimulation by PGE₂ was almost completed abrogated in constructs that included 2-bp mutations in either the CRE and FRE. In gel shift analyses an increased binding of nuclear extract components to double-stranded oligonucleotide probes containing CRE and FRE was observed following treatment with PGE₂. These studies show that PGE₂ induces BSP transcription in UMR 106 cells through juxtaposed CRE and FRE elements in the proximal promoter of the BSP gene.
Tyrosine phosphorylation is involved in Ca<sup>2+</sup>entry in human gingival fibroblasts
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Bradykinin (1 μM) and histamine (100 μM) evoked an initial transient increase and a subsequent sustained increase in intracellular Ca²⁺concentration ([Ca²⁺]_i) in fura-2-loaded human gingival fibroblasts, which may be attributed to Ca²⁺release from intracellular stores and Ca²⁺entry from extracellular sites, respectively. In fibroblasts pretreated with tyrosine kinase inhibitors such as herbimycin A (1 μM) and tyrphostin 47 (20 μM)_,the sustained level of [Ca²⁺]_iinduced by bradykinin and histamine increased, but not the initial peak level. In the absence of external Ca²⁺, bradykinin and histamine induced only the transient increase in [Ca²⁺]_i, but a subsequent addition of Ca²⁺to the medium resulted in a sustained increase in [Ca²⁺]_icaused by Ca²⁺entry. Thapsigargin, an inhibitor of Ca²⁺-ATPase in inositol 1,4,5-trisphosphate-sensitive Ca²⁺stores, mimicked the effect of bradykinin and histamine. In the fibroblasts pretreated with tyrosine kinase inhibitors, the bradykinin-, histamine- and thapsigargin-induced Ca²⁺entry was clearly enhanced, but not the transient [Ca²⁺]_iincrease. Tyrosine phosphatase inhibitor benzylphosphonic acid (200 μM) had no effect on Ca²⁺entry or transient [Ca²⁺]_iincrease. These results suggest that tyrosine phosphorylation is involved in Ca²⁺entry in human gingival fibroblasts.
Thrombin-induced Ca<sup>2+</sup> mobilization in human gingival fibroblasts is mediated by protease-activated receptor-1 (PAR-1)
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By reverse transcription (RT)-PCR analyses, human gingival fibroblasts (HGFs) were demonstrated to express mRNAs for protease-activated receptor-1 (PAR-1) and PAR-3, although the expression of PAR-3 was much weaker than that of PAR-1. The mRNAs for PAR-2 and PAR-4 were not found by RT-PCR. Furthermore, PAR activation was studied by monitoring cytosolic Ca²⁺ concentration ([Ca²⁺]i) in cultured HGFs loaded with fura-2. At concentrations > 0.1 nM, α-thrombin caused a transient increase in [Ca²⁺]i in a concentration-dependent manner, and the maximum response was obtained with 10 nM α-thrombin. After the [Ca²⁺]i response, the HGFs were completely desensitized to the second stimulation with α-thrombin. The PAR-1 agonist peptide SFLLRN produced approximately the same transient [Ca²⁺]i response as α-thrombin. After stimulation with SFLLRN, the HGFs did not respond to α-thrombin, indicating that treatment with SFLLRN results in complete desensitization to α-thrombin. The PAR-2 and PAR-4 agonist peptides had no effect on [Ca²⁺]i in HGFs. These results suggest that α-thrombin-induced Ca²⁺ mobilization in HGFs is solely mediated by PAR-1.

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^☆: This work was supported by a Grant-in-Aid for Scientific Research (No. 04771546) from the Ministry of Education, Science and Culture of Japan (N. Niisato), a Nihon university Research Grant in 1994, and MPG Corporation research funds.

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Research paperHistamine H1 receptor-induced Ca2+ mobilization and prostaglandin E2 release in human gingival fibroblasts: Possible role of receptor-operated Ca2+ influx☆

Abstract

J Theor Biol

Exp Cell Res

Cytokine

J Biol Chem

J Biol Chem

Biochem Biophys Res Commun

J Biol Chem

J Biol Chem

Trends Pharmacol Sci

Developmental patterns of histamine-like immunoreactivity in the mouse

J Histochem Cytochem

Immediate hypersensitivity and periodontal disease

J Periodontol

Histamine receptors in human fibroblasts: Inositol phosphates, Ca2+, and cell growth

Am J Physiol

Histamine as a growth factor and chemoattractant for human carcinoma and melanoma cells: Action through Ca2+-mobilizing H1 receptors

J Cell Biol

The mechanism of basophil histamine release in patients with periodontal disease

Clin Exp Immunol

Release processes in mast cells and their activation by injury

Ann NY Acad Sci

Diabetes and periodontal disease. Possible role of vitamin C deficiency: An hypothesis

J Periodontol

Mast cells of the human gingiva

J Periodont Res

Research paper
Histamine H₁ receptor-induced Ca²⁺ mobilization and prostaglandin E₂ release in human gingival fibroblasts: Possible role of receptor-operated Ca²⁺ influx☆

Histamine receptors in human fibroblasts: Inositol phosphates, Ca²⁺, and cell growth

Histamine as a growth factor and chemoattractant for human carcinoma and melanoma cells: Action through Ca²⁺-mobilizing H₁ receptors