Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This work aimed to investigate the molecular role of gastrin in histamine synthesis in isolated rabbit fundic mucosal cells enriched in enterochromaffin-like (ECL) cells (37%). Gastrin stimulated histidine decarboxylase (HDC) activity by increasing the maximal velocity (Vmax) from 0.240 +/- 0.017 (basal value) to 0.332 +/- 0.012 pmol/mg protein/h and by decreasing the Michaelis-Menten constant value -Km; 73.90 +/- 2.2 vs. 93.42 +/- 4.32 microM (basal value)]. Pertussis toxin (PTX) (200 ng/ml) reduced the stimulation of HDC induced by 10 nM gastrin from 41.8 to 15.9%, whereas cholera toxin (CTX) (100 ng/ml) was without effect. Staurosporine and polymyxin B inhibited in a dose dependent manner the HDC activity stimulated by 10 nM gastrin. Phorbol 12-myristate 13-acetate (PMA; 100 nM) decreased Vmax (0.558 +/- 0.021 pmol/ mg protein/h) but did not change the Km. Furthermore, cycloheximide (0.1-10 microM) inhibited the gastrin-induced stimulation of HDC activity, whereas actinomycin D (up to 10 microM) was without effect. Finally, incubation of cells with gastrin (10 microM) left the expression of HDC mRNA unchanged. We concluded that gastrin, acting through "gastrin/CCK-B type" receptors coupled to PTX-sensitive G protein, exerts a short-term regulation of histamine synthesis in gastric ECL cells by increasing both the affinity of HDC for L-histidine and the number of active enzyme molecules. This last event, related to protein kinase C activation, could be due to a translational or posttranslational mechanism.
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PMID:Gastrin stimulation of histamine synthesis in enterochromaffin-like cells from rabbit fundic mucosa. 863 12

In this study we investigated the short-term effect of somatostatin on histamine synthesis in a cell population isolated from rabbit gastric mucosa and enriched in enterochromaffin-like cells. Somatostatin inhibited basal and gastrin-stimulated histamine synthesis through a dual mechanism involving a decrease in the affinity of histidine decarboxylase (HDC) for its substrate (L-histidine) and a reduction in the number of functional HDC molecules. H-89 (an inhibitor of cAMP-dependent protein kinase) mimicked somatostatin-induced reduction of HDC affinity, which, on the contrary, was selectively reversed by pertussis toxin (PTX). Furthermore, forskolin was shown to reverse the inhibitory effect of H-89 and to prevent the somatostatin-induced reduction in HDC affinity for L-histidine. Thus, the somatostatin-induced reduction in affinity seems to involve a PTX-sensitive G protein and an inhibition of the cAMP-dependent pathway. On the other hand, the somatostatin-induced decrease in the number of functional HDC molecules seems to be PTX insensitive and independent from a modulation of the cAMP pathway, and does not seem to involve a significant change in HDC messenger RNA expression or a regulation of protein kinase C. The exact nature of this second mechanism will need further studies to be elucidated.
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PMID:Short-term inhibitory effect of somatostatin on gastric histamine synthesis. 904 95

The effects of histamine on high-voltage-activated Ca2+ channels in the histaminergic neurons acutely dissociated from the rat tuberomammillary nucleus were investigated in the nystatin-perforated patch recording mode under voltage-clamp conditions. Histamine suppressed the high-voltage-activated Ca2+ channel currents in neurons which were positive for histidine decarboxylase with immunocytochemistry. The half-maximum inhibitory concentration and maximum inhibition were 2.6 x 10(-7) M and 16.6+/-1.90%, respectively. An H3 receptor agonist, R(-)-alpha-methylhistamine, mimicked the response to histamine, and thioperamide, an H3 receptor antagonist, inhibited the response to histamine. On the other hand, neither 2-methylhistamine, an H1 receptor agonist, nor dimaprit, an H2 receptor agonist, had a significant effect on the Ca2+ channel currents. Pretreatment with pertussis toxin blocked the inhibitory effect of histamine on Ca2+ channels, suggesting the involvement of Gi/Go proteins in the action of histamine. Omega-conotoxin-GVIA, omega-agatoxin-IVA, nicardipine, and omega-conotoxin-MVIIC blocked the high-voltage-activated Ca2+ channel currents by 15.6, 4.3, 27.1, and 31.2% of the total current, respectively, suggesting the existence of N-, P-, L-, and Q-type Ca2+ channels. A current that was insensitive to these blockers was also found. This residual current, "R-type", was completely suppressed by the addition of 200 microM Cd2+. Histamine significantly inhibited both the N- and P-type current components among these five types of Ca2+ channel currents. We concluded that histamine suppresses the N- and P-type Ca2+ channels in histaminergic neurons through an H3 receptor which is linked to a pertussis toxin-sensitive G-protein.
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PMID:Histamine modulates high-voltage-activated calcium channels in neurons dissociated from the rat tuberomammillary nucleus. 975 67

H(3) autoreceptors provide feedback control of neurotransmitter synthesis in histaminergic neurons, but the transduction pathways involved are poorly understood. In rat brain cortical slices, histamine synthesis can be stimulated by depolarization and inhibited by H(3) agonists. We show that histamine synthesis stimulation by depolarization with 30 mM K(+) requires extracellular calcium entry, mostly through N-type channels, and subsequent activation of calcium/calmodulin-dependent protein kinase type II. In vitro, this kinase phosphorylated and activated histidine decarboxylase, the histamine-synthesizing enzyme. Inhibition of depolarization-stimulated histamine synthesis by the histamine H(3) receptor agonist imetit was impaired by preincubation with pertussis toxin and by the presence of a myristoylated peptide (myristoyl-N-QEHAQEPERQYMHIGTMVE-FAYALVGK) blocking the actions of G-protein betagamma subunits. The stimulation of another G(i/o)-coupled receptor, adenosine A(1), also decreased depolarization-stimulated histamine synthesis. In contrast, protein kinase A activation, which is also repressed by H(3) receptors, elicited a depolarization- and calcium/calmodulin-independent stimulation of histamine synthesis. Protein kinase A was able also to phosphorylate and activate histidine decarboxylase in vitro. These results show how depolarization activates histamine synthesis in nerve endings and demonstrate that both pathways modulating neurotransmitter synthesis are controlled by H(3) autoreceptors.
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PMID:H3 autoreceptors modulate histamine synthesis through calcium/calmodulin- and cAMP-dependent protein kinase pathways. 1546 23

The present study was undertaken to investigate the involvement of chemical mediators in nasal allergic responses using histidine decarboxylase knockout (HDC-KO) mice. An allergic rhinitis model was developed in HDC-KO and wild-type mice by the intraperitoneal injection of ovalbumin, aluminum hydroxide gel and pertussis toxin. Five days later, they were boosted by a subcutaneous injection of ovalbumin into the back. From day 18 after the first immunization to day 39, intranasal sensitization with ovalbumin was performed every day and the severity of allergic rhinitis was observed by measuring nasal allergic responses and total IgE levels. It was found that the intranasal administration of antigen caused a significant increase of nasal sneezing and rubbing from day 25 to day 39 both in sensitized HDC-KO and wild-type mice. In addition, a significant elevation of total IgE levels in serum was also found both in sensitized HDC-KO and wild-type mice from day 18 to day 39 after the first immunization. L-733,060, a tachykinin NK(1) receptor antagonist at a dose of 10 mg/kg (s.c.), resulted in the dose-dependent inhibition of nasal allergic responses induced by antigen in both HDC-KO and wild-type mice. In addition, both chlorpheniramine at doses of 3 and 10 mg/kg (p.o.) and BW A868C at doses of 0.3 and 1 mg/kg (i.v.) also showed a dose-related reduction of the nasal allergic responses induced by antigen in sensitized wild-type mice. On the other hand, they had no effects on the nasal signs induced by antigen in HDC-KO mice. From these results, it was revealed that substance P induces nasal allergic responses in the mouse model of chronic allergic rhinitis through the activation of tachykinin NK(1) receptors. Therefore, it can be concluded that not only histamine, but also substance P and prostaglandin D(2), participated in the nasal allergic responses induced by antigen in mice.
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PMID:Involvement of chemical mediators in nasal allergic responses of HDC-KO mice. 1754

Induction of T helper 1 (Th1) to Th2 deviation through administration of self- or altered self-peptides holds promise for treatment of autoimmunity. However, administration of self-peptides in models of autoimmunity can result in anaphylactic reactions. Although both IgE and IgG1 antibodies might be involved in the development of anaphylaxis to myelin peptides in experimental autoimmune encephalomyelitis in mice, the effector cells and molecules involved are not fully understood. Here we show that systemic anaphylaxis to the self-antigen myelin oligodendrocyte glycoprotein (MOG) 35-55 can occur in mice lacking mast cells (Kit(W)/Kit(W-v) mice) or histamine (histidine decarboxylase-deficient mice), but is prevented in mice lacking IL-4. Treatment of mice with CV6209, a platelet-activating factor antagonist, slightly reduced the incidence of anaphylaxis to self-MOG35-55 in this model, but more effectively protected mice against anaphylaxis to this peptide when self-MOG35-55 was administered in a different immunization protocol that omitted the use of Bordetella pertussis toxin as an adjuvant at the time of immunization. Thus, anaphylactic reactions to self-MOG can occur in the absence of mast cells or histamine, key elements of the classical IgE-, mast cell-, and histamine-dependent pathway of anaphylaxis.
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PMID:Anaphylaxis to a self-peptide in the absence of mast cells or histamine. 1918 9

PGE2 has long been known as a potentiator of acute inflammation, but its mechanisms of action still remain to be defined. In this study, we employed inflammatory swelling induced in mice by arachidonate and PGE2 as models and dissected the role and mechanisms of action of each EP receptor at the molecular level. Arachidonate- or PGE2-induced vascular permeability was significantly reduced in EP3-deficient mice. Intriguingly, the PGE2-induced response was suppressed by histamine H1 antagonist treatment, histidine decarboxylase deficiency, and mast cell deficiency. The impaired PGE2-induced response in mast cell-deficient mice was rescued upon reconstitution with wild-type mast cells but not with EP3-deficient mast cells. Although the number of mast cells, protease activity, and histamine contents in ear tissues in EP3-deficient mice were comparable to those in wild-type mice, the histamine contents in ear tissues were attenuated upon PGE2 treatment in wild-type but not in EP3-deficient mice. Consistently, PGE2-EP3 signaling elicited histamine release in mouse peritoneal and bone marrow-derived mast cells, and it exerted degranulation and IL-6 production in a manner sensitive to pertussis toxin and a PI3K inhibitor and dependent on extracellular Ca(2+) ions. These results demonstrate that PGE2 triggers mast cell activation via an EP3-Gi/o-Ca(2+) influx/PI3K pathway, and this mechanism underlies PGE2-induced vascular permeability and consequent edema formation.
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PMID:Prostaglandin E2-EP3 signaling induces inflammatory swelling by mast cell activation. 2434 6