-Fluoromethylhistidine elevates histidine decarboxylase mRNA and chromogranin A mRNA levels in rat oxyntic mucosa

1997 ◽  
Vol 46 (0) ◽  
pp. 107-108 ◽  
Author(s):  
E. Lindström ◽  
K. Andersson, D. Chen ◽  
H.-J. Monstein, Å. Boketoft ◽  
R. Håkanson
Keyword(s):  
Chromogranin A ◽  
Histidine Decarboxylase ◽  
Mrna Levels ◽  
Oxyntic Mucosa

scholarly journals Amino- and Carboxy-Terminal PEST Domains Mediate Gastrin Stabilization of Rat l-Histidine Decarboxylase Isoforms

2000 ◽  
Vol 20 (13) ◽  
pp. 4932-4947 ◽  
Author(s):  
John V. Fleming ◽  
Timothy C. Wang
Keyword(s):  
Histidine Decarboxylase ◽  
Chimeric Protein ◽  
Proteasome Inhibition ◽  
Peptide Hormone ◽  
Mrna Levels ◽  
Intracellular Targeting ◽  
Enzymatic Function ◽  
Steady State Levels ◽  
The Stability ◽  
Carboxy Terminal

ABSTRACT Control of enzymatic function by peptide hormones can occur at a number of different levels and can involve diverse pathways that regulate cleavage, intracellular trafficking, and protein degradation. Gastrin is a peptide hormone that binds to the cholecystokinin B-gastrin receptor and regulates the activity ofl-histidine decarboxylase (HDC), the enzyme that produces histamine. Here we show that gastrin can increase the steady-state levels of at least six HDC isoforms without affecting HDC mRNA levels. Pulse-chase experiments indicated that HDC isoforms are rapidly degraded and that gastrin-dependent increases are due to enhanced isoform stability. Deletion analysis identified two PEST domains (PEST1 and PEST2) and an intracellular targeting domain (ER2) which regulate HDC protein expression levels. Experiments with PEST domain fusion proteins demonstrated that PEST1 and PEST2 are strong and portable degradation-promoting elements which are positively regulated by both gastrin stimulation and proteasome inhibition. A chimeric protein containing the PEST domain of ornithine decarboxylase was similarly affected, indicating that gastrin can regulate the stability of other PEST domain-containing proteins and does so independently of antizyme/antizyme inhibitor regulation. At the same time, endoplasmic reticulum localization of a fluorescent chimera containing the ER2 domain of HDC was unaltered by gastrin stimulation. We conclude that gastrin stabilization of HDC isoforms is dependent upon two transferable and sequentially unrelated PEST domains that regulate degradation. These experiments revealed a novel regulatory mechanism by which a peptide hormone such as gastrin can disrupt the degradation function of multiple PEST-domain-containing proteins.

scholarly journals Glucocorticoid hormones downregulate histidine decarboxylase mRNA and enzyme activity in rat lung

1998 ◽  
Vol 275 (2) ◽  
pp. L407-L413 ◽  
Author(s):  
Cynthia A. Zahnow ◽  
Pertti Panula ◽  
Atsushi Yamatodani ◽  
David E. Millhorn
Keyword(s):  
Gene Expression ◽  
Enzyme Activity ◽  
Adrenal Gland ◽  
Histidine Decarboxylase ◽  
Mrna Levels ◽  
Glucocorticoid Hormones ◽  
Rat Lung ◽  
Dexamethasone Treatment ◽  
Inflammatory Disorders ◽  
Corticosterone Treatment

Histidine decarboxylase (HDC) is the primary enzyme regulating histamine biosynthesis. Histamine contributes to the pathogenesis of chronic inflammatory disorders such as asthma. Because glucocorticoids are effective in the treatment of asthma, we examined the effects of 6 h of exogenously administered dexamethasone (0.5–3,000 μg/kg ip), corticosterone (0.2–200 mg/kg ip), or endogenously elevated corticosterone (via exposure of rats to 10% oxygen) on HDC expression in the rat lung. HDC transcripts were decreased ∼73% with dexamethasone treatment, 57% with corticosterone treatment, and 50% with exposure to 10% oxygen. Likewise, HDC enzyme activity was decreased 80% by treatment with dexamethasone and corticosterone and 60% by exposure to 10% oxygen. Adrenalectomy prevented the decreases in HDC mRNA and enzyme activity observed in rats exposed to 10% oxygen, suggesting that the adrenal gland is necessary for the mediation of hypoxic effects on HDC gene expression. These results demonstrate that corticosteroids initiate a process that leads to the decrease of HDC mRNA levels and enzyme activity in rat lung.

Differentiation of the Gastric Mucosa I. Role of histamine in control of function and integrity of oxyntic mucosa: understanding gastric physiology through disruption of targeted genes

2006 ◽  
Vol 291 (4) ◽  
pp. G539-G544 ◽  
Author(s):  
Duan Chen ◽  
Takeshi Aihara ◽  
Chun-Mei Zhao ◽  
Rolf Håkanson ◽  
Susumu Okabe
Keyword(s):  
Gastric Mucosa ◽  
Histidine Decarboxylase ◽  
Parietal Cells ◽  
Oxyntic Mucosa ◽  
Mucosal Integrity ◽  
Ecl Cells ◽  
Gastric Physiology ◽  
Ecl Cell ◽  
Insight Into

Many physiological functions of the stomach depend on an intact mucosal integrity; function reflects structure and vice versa. Histamine in the stomach is synthesized by histidine decarboxylase (HDC), stored in enterochromaffin-like (ECL) cells, and released in response to gastrin, acting on CCK2 receptors on the ECL cells. Mobilized ECL cell histamine stimulates histamine H2 receptors on the parietal cells, resulting in acid secretion. The parietal cells express H2, M3, and CCK2 receptors and somatostatin sst2 receptors. This review discusses the consequences of disrupting genes that are important for ECL cell histamine release and synthesis (HDC, gastrin, and CCK2 receptor genes) and genes that are important for “cross-talk” between H2 receptors and other receptors on the parietal cell (CCK2, M3, and sst2 receptors). Such analysis may provide insight into the functional significance of gastric histamine.

scholarly journals Histidine decarboxylase expression and histamine metabolism in gastric oxyntic mucosa during hypergastrinemia and carcinoid tumor formation.

Endocrinology ◽  
1996 ◽  
Vol 137 (10) ◽  
pp. 4435-4442 ◽  
Author(s):  
L Kölby ◽  
B Wängberg ◽  
H Ahlman ◽  
I M Modlin ◽  
G Granérus ◽  
...  
Keyword(s):  
Carcinoid Tumor ◽  
Histidine Decarboxylase ◽  
Tumor Formation ◽  
Histamine Metabolism ◽  
Oxyntic Mucosa

Immunolocalization of gastrin-dependent histidine decarboxylase activity in rat gastric mucosa during feeding

1998 ◽  
Vol 275 (4) ◽  
pp. G660-G667 ◽  
Author(s):  
Gordon V. Ohning ◽  
Min Song ◽  
Helen C. Wong ◽  
S. Vincent Wu ◽  
John H. Walsh
Keyword(s):  
Enzyme Activity ◽  
Histidine Decarboxylase ◽  
Gastric Gland ◽  
Decarboxylase Activity ◽  
Rapid Reduction ◽  
Oxyntic Mucosa ◽  
Ecl Cells ◽  
Rat Gastric Mucosa ◽  
Fasting And Refeeding ◽  
Atropine Treatment

The localization of histidine decarboxylase (HDC) activity in the enterochromaffin-like (ECL) cells of the oxyntic mucosa was studied during fasting and refeeding using monoclonal (CURE no. 44178) and polyclonal (CURE no. 94211) antibodies directed against the COOH terminus of HDC (HDC-CT). Changes in HDC immunostaining were correlated with mucosal HDC enzyme activity. Immunoneutralization of circulating gastrin and atropine treatment during refeeding were used to determine the relative importance of gastrin and cholinergic mechanisms in the regulation of HDC activity and immunostaining. Fasting caused a rapid reduction in the number of ECL cells immunostaining for HDC that was correlated with an almost complete loss of mucosal HDC enzyme activity. Refeeding restored both HDC immunostaining and enzyme activity within 2–4 h, and this response was inhibited by gastrin immunoneutralization but not by atropine treatment. Immunostaining was uniformly decreased and restored in the lower half of the oxyntic mucosa, which corresponds to the predominant area of ECL cells in the gastric gland. Histamine immunostaining and mucosal histamine content were not significantly changed during fasting and refeeding or by gastrin antibody and/or atropine treatment during refeeding. These findings indicate that HDC activity correlates with HDC-CT immunostaining and that both HDC activity and HDC-CT immunostaining are regulated by gastrin during refeeding.

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