Histamine content, synthesis and degradation in nasal mucosa and lung of guinea‐pigs treated with toluene diisocyanate (TDI)

Abe, Yoshiyuki; Ogino, Satoshi; Irifune, Morihiro; Imamura, Ikuo; Liu, Y. Q.; Fukui, Hirokazu; Matsunaga, Toru

doi:10.1111/j.1365-2222.1993.tb03239.x

Cited by 35 publications

(24 citation statements)

References 23 publications

(26 reference statements)

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“…Our previous works (7,8) have demonstrated that repeated intranasal application of toluene 2,4-diisocyanate (TDI) induced release of histamine from mast cells via neurogenic inflammation and leads to the development of nasal hypersensitivity behavior in guinea pigs. We also showed that both H1R mRNA and H1R protein level were up-regulated in TDI sensitized allergic rats and H1R mRNA was significantly suppressed by the treatment of d-chlorpheniramine, an H1R antagonist (9).…”

Section: Introductionmentioning

confidence: 99%

Stimulation of Histamine H1 Receptor Up-Regulates Histamine H1 Receptor Itself Through Activation of Receptor Gene Transcription

et al. 2007

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Abstract. Histamine is a major mediator in allergy acting mainly through the histamine H 1 receptor (H1R). Although H1R up-regulation has been suggested as an important step for induction of allergic symptoms, little is known about the regulation of H1R level. Here we report that the activation of H1R up-regulates H1R through augmentation of H1R mRNA expression in HeLa cells. Histamine stimulation significantly increased both H1R promoter activity and mRNA level without alteration in mRNA stability. H1R protein was also up-regulated by histamine. An H1R antagonist but not histamine H 2 receptor antagonist blocked histamine-induced up-regulation of both promoter activity and mRNA expression. A protein kinase C (PKC) activator, phorbol-12-myristate-13-acetate, increased H1R mRNA expression, whereas an activator of PKA or PKG (8-Br-cAMP or 8-Br-cGMP, respectively) did not. Furthermore, histamine-induced upregulation of both promoter activity and mRNA level were completely suppressed by the PKC inhibitor Ro-31-8220. H1R antagonists have long been thought to block H1R and inhibit immediate allergy symptoms. In addition to this short-term effect, our data propose their longterm inhibitory effect against allergic diseases by suppressing PKC-mediated H1R gene transcription. This finding provides new insights into the therapeutic target of H1R antagonist in allergic diseases.

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Section: Introductionmentioning

confidence: 99%

Stimulation of Histamine H1 Receptor Up-Regulates Histamine H1 Receptor Itself Through Activation of Receptor Gene Transcription

et al. 2007

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“…We have demonstrated that intranasal application of toluene-2,4-diisocyanate (TDI) induces histamine release from mast cells via neurogenic inflammation and causes nasal hypersensitivity in rats (5), with H1R expression being up-regulated at both the mRNA and protein levels in the nasal mucosa of TDI-sensitized rats (6). We have also demonstrated that the level of H1R expression is strongly correlated with the severity of allergy symptoms in TDIsensitized rats and in patients with pollinosis (7), while agents that suppress H1R gene up-regulation alleviate allergy symptoms (8,9).…”

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confidence: 99%

Inverse Agonistic Activity of Antihistamines and Suppression of Histamine H1 Receptor Gene Expression

et al. 2012

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Pollinosis is a seasonal allergic rhinitis caused by hypersensitivity to tree or grass pollens, which affects more than 36 million people in the U.S. and about 16% of the Japanese population (1, 2). Histamine is a major chemical mediator involved in allergic reactions. Its actions are mainly mediated by the histamine H 1 receptor (H1R) and H1R activation results in the symptoms of allergic rhinitis.It has been reported that expression of H1R mRNA is increased in patients with allergic rhinitis (3,4). We have demonstrated that intranasal application of toluene-2,4-diisocyanate (TDI) induces histamine release from mast cells via neurogenic inflammation and causes nasal hypersensitivity in rats (5), with H1R expression being up-regulated at both the mRNA and protein levels in the nasal mucosa of TDI-sensitized rats (6). We have also demonstrated that the level of H1R expression is strongly correlated with the severity of allergy symptoms in TDIsensitized rats and in patients with pollinosis (7), while agents that suppress H1R gene up-regulation alleviate allergy symptoms (8, 9). These findings, combined with the report that the strength of H1R signaling depends on the level of expression of this receptor (10), suggest that H1R is an allergy-sensitive gene and that its expression influences the severity of allergy symptoms. Therefore, drugs targeting the signaling pathway involved in histamine-induced up-regulation of H1R gene expression could be useful for treating allergic diseases.Antihistamines are widely employed as the first-line treatment for nasal symptoms of pollinosis because these drugs are thought to antagonize histamine and prevent it from binding to the H1R. According to the two-state model, however, the active and inactive states of a receptor exist in equilibrium, so antihistamines could act as inverse agonists that combine with and stabilize the inactive form of H1R to shift the equilibrium toward the inactive state and down-regulate constitutive receptor activity, even in the absence of histamine (11). Therefore, antihistamines might not only antagonize histamine by blocking its binding with the H1R, but could also suppress constitutive H1R activity. Although the clinical importance of constitutive activity has not been clarified, it can be hypothesized that inverse agonists would more potently alleviate allergic symptoms than neutral antagonists by inhibiting constitutive activity. However, the influence of the inverse agonistic activity of antihistamines on H1R gene expression has not been evaluated.We previously demonstrated that histamine stimulates up-regulation of H1R gene expression in HeLa cells that endogenously express this receptor (6). In the present study, we examined the effect of inverse agonists on upregulation of H1R gene expression by HeLa cells. Our Tokushima 770-8505, Japan Received September 29, 2011; Accepted November 15, 2011 Abstract. Histamine H 1 receptor (H1R) expression influences the severity of allergy symptoms. We examined the effect of inverse agonists on H1R g...

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“…and plasma extravasation (Sekizawa et al in press), indicating that HMT is highly active and is more important than DAO in limiting the biological action of histamine, as is also true in brain (Burkard et al 1963;Schwartz 1977). In fact, biochemical studies demonstrate that the HMT activity is higher than DAO activity by 13 times in the guinea pig lung (Abe et al 1993a) and by 50 times in the human nasal mucosa (Abe et al 1993b). Furthermore, histamine content and HMT activity increased in the nasal mucosa and lung of toluene diisocyanate (TDI )-sensitized guinea pigs, whereas the DAO activity did not (Abe et al 1993a).…”

Section: Histamine Synthesis and Metabolismmentioning

confidence: 99%

“…In fact, biochemical studies demonstrate that the HMT activity is higher than DAO activity by 13 times in the guinea pig lung (Abe et al 1993a) and by 50 times in the human nasal mucosa (Abe et al 1993b). Furthermore, histamine content and HMT activity increased in the nasal mucosa and lung of toluene diisocyanate (TDI )-sensitized guinea pigs, whereas the DAO activity did not (Abe et al 1993a). …”

Section: Histamine Synthesis and Metabolismmentioning

confidence: 99%

Enzymatic Modulation of Bronchoconstriction, Gland Secretion, Plasma Extravasation and Cough.

Sekizawa

1994

Tohoku J. Exp. Med.

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Histamine content, synthesis and degradation in nasal mucosa and lung of guinea‐pigs treated with toluene diisocyanate (TDI)

Cited by 35 publications

References 23 publications

Stimulation of Histamine H1 Receptor Up-Regulates Histamine H1 Receptor Itself Through Activation of Receptor Gene Transcription

Stimulation of Histamine H1 Receptor Up-Regulates Histamine H1 Receptor Itself Through Activation of Receptor Gene Transcription

Inverse Agonistic Activity of Antihistamines and Suppression of Histamine H1 Receptor Gene Expression

Enzymatic Modulation of Bronchoconstriction, Gland Secretion, Plasma Extravasation and Cough.

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