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

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.

Download Full-text

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

Inflammation Research ◽

10.1007/s000110050124 ◽

1997 ◽

Vol 46 (0) ◽

pp. 107-108 ◽

Cited By ~ 2

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

Download Full-text

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

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1998.275.4.g660 ◽

1998 ◽

Vol 275 (4) ◽

pp. G660-G667 ◽

Cited By ~ 4

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.

Download Full-text

Comparison between activation of ornithine decarboxylase and histidine decarboxylase in rat stomach

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1996.270.3.g476 ◽

1996 ◽

Vol 270 (3) ◽

pp. G476-G486 ◽

Cited By ~ 1

Author(s):

X. Q. Ding ◽

D. Chen ◽

E. Rosengren ◽

L. Persson ◽

R. Hakanson

Keyword(s):

Food Intake ◽

Ornithine Decarboxylase ◽

Histidine Decarboxylase ◽

Serum Gastrin ◽

Oral Treatment ◽

Somatostatin Analogue ◽

Rat Stomach ◽

Oxyntic Mucosa ◽

Serum Gastrin Concentration ◽

Fasted Rats

We compared the responses of rat stomach ornithine decarboxylase (ODC) and histidine decarboxylase (HDC) to food intake, oral treatment with antisecretagogues, NaHCO3, and hypertonic NaCl, antrectomy, intravenous infusion of gastrin-17, the selective cholecystokinin (CCK)-B/gastrin receptor antagonist L-365,260, and the somatostatin analogue RC-160. The serum gastrin concentration and oxyntic mucosal ODC and HDC activities were higher in freely fed rats than in fasted rats. Food intake in fasted rats raised the serum gastrin concentration and the ODC and HDC activities. Ranitidine, omeprazole, and NaHCO3 raised the serum gastrin concentration and activated ODC and HDC. Hypertonic NaCl raised the ODC activity 200-fold, whereas circulating gastrin and HDC activity were increased only moderately. Infusion of gastrin-17 activated HDC but not ODC. L-365,260 prevented the activation of HDC but not of ODC in response to food intake and treatment with omeprazole, NaHCO3, or hypertonic NaCl. Antrectomy prevented the food- and omeprazole-evoked rise in oxyntic mucosal HDC activity but not the rise in ODC activity. RC-160 suppressed HDC activity after food intake and treatment with omeprazole, NaHCO3, or NaCl. In contrast, RC-160 suppressed omeprazole- and NaHCO3-evoked ODC activation but not that evoked by food intake or NaCl. The results support the view that HDC in the oxyntic mucosa is activated by gastrin and suppressed by somatostatin. The induction of ODC is not mediated by gastrin; ODC activation appears to be related to acid inhibition per se or to mucosal maintenance and repair; somatostatin, or rather the lack of it, might contribute to the induction of ODC after acid blockade. The mechanism behind the activation of rat stomach ODC seems to differ depending on the type of stimulus.

Download Full-text

Gastrin regulates histidine decarboxylase activity and mRNA abundance in rat oxyntic mucosa

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1994.267.2.g254 ◽

1994 ◽

Vol 267 (2) ◽

pp. G254-G258 ◽

Cited By ~ 9

Author(s):

A. K. Sandvik ◽

R. Dimaline ◽

R. Marvik ◽

E. Brenna ◽

H. L. Waldum

Keyword(s):

Enzymatic Activity ◽

Histidine Decarboxylase ◽

Serum Gastrin ◽

Mrna Abundance ◽

Decarboxylase Activity ◽

Oxyntic Mucosa ◽

Trophic Effect ◽

Ecl Cell ◽

Release Histamine ◽

Different Doses

Gastrin release histamine from the oxyntic mucosa, stimulates the enzymatic activity of histidine decarboxylase (HDC), increases HDC mRNA abundance, and has a trophic effect on the enterochromaffin-like (ECL) cell. In the present study, we examined the effect of exogenous gastrin on HDC activity and mRNA and the time scale of increase and decline of HDC activity and mRNA. Rats received intravenous infusion of gastrin-(1-17) in different doses or periods of time. Oxyntic mucosal HDC activity and mRNA abundance increased significantly with serum gastrin concentrations in the physiological range. The onset of response was rapid and maximal for both parameters after 2 h. Poststimulatory decrease was maximal 2 h after cessation of gastrin infusion. Those observations suggest that HDC enzymatic activity and mRNA abundance are important in meal-to-meal regulation of gastric secretion. Furthermore, HDC enzymatic activity and mRNA abundance varied in parallel, indicating that HDC mRNA abundance is important in the overall regulation of gastric mucosal HDC activity.

Download Full-text

Effects of dexamethasone on the activity of histidine decarboxylase, ornithine decarboxylase, and DOPA decarboxylase in rat oxyntic mucosa

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y91-006 ◽

1991 ◽

Vol 69 (1) ◽

pp. 37-42 ◽

Cited By ~ 12

Author(s):

Masataka Araki ◽

Mitsuo Nakamura ◽

Seiichi Takenoshita ◽

Hirokazu Shoda ◽

Yukio Nagamachi ◽

...

Keyword(s):

Ornithine Decarboxylase ◽

Histidine Decarboxylase ◽

Serum Gastrin ◽

Single Injection ◽

Dopa Decarboxylase ◽

Peptic Ulcers ◽

Dexamethasone Treatment ◽

Oxyntic Mucosa ◽

Significant Change ◽

Stimulation Of

Since accelerated turnover of histamine in oxyntic mucosa may be an important factor in the pathogenesis of peptic ulcers, the effect of dexamethasone and other glucocorticoids on the activity of gastric histidine decarboxylase (HDC) was studied in the rat. The activity of HDC in rat oxyntic mucosa increased significantly after dexamethasone was injected s.c. to rats at doses larger than 0.4 mg/kg body weight. The maximum response of the HDC activity to dexamethasone (4 mg/kg) was observed 8 h after the treatment. The activity of ornithine decarboxylase (ODC) increased at 4 h, while that of DOPA decarboxylase showed no significant change throughout the 16-h period following a single injection of dexamethasone. The mucosal levels of histamine, putrescine, and spermidine rose significantly after the steroid treatment, while the spermine levels remained nearly constant. There was no sex difference in these responses to dexamethasone. Betamethasone showed nearly the same effects as dexamethasone on the decarboxylase activities and the mucosal levels of diamines. Serum gastrin levels showed no significant change for the first 4 h and then rose significantly 8 and 16 h after dexamethasone treatment. Pentagastrin (0.5 mg/kg) increased the HDC activity, while it showed no significant effect on either the mucosal ODC activity or levels of polyamines and histamine. These data suggest that dexamethasone influences the metabolism of histamine and polyamines in rat oxyntic mucosa both directly and via stimulation of gastrin release.Key words: dexamethasone, betamethasone, oxyntic mucosa, histidine decarboxylase, ornithine decarboxylase, DOPA decarboxylase.

Download Full-text

Effect of Derivatives and Inhibitors of Histamine Metabolism on Gastric Secretion

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1958.195.2.521 ◽

1958 ◽

Vol 195 (2) ◽

pp. 521-524 ◽

Cited By ~ 12

Author(s):

A. C. Ivy ◽

K. W. Liepins

Keyword(s):

Gastric Secretion ◽

Diamine Oxidase ◽

Histidine Decarboxylase ◽

Secretory Activity ◽

Histamine Metabolism ◽

Oxidative Deamination ◽

Additional Advantage ◽

Heidenhain Pouch ◽

First Derivative ◽

Derivatives Of

Since the derivatives of histamine metabolism are quite well known, those which have been synthesized were tested for gastric secretory activity in Heidenhain pouch dogs. All were inactive in a single total dose of 20 mg or 1.7 mg/kg. N-acetylhistamine is 1000 times less active than histamine. 1-Methyl-4-(aminoethyl) imidazole, the first derivative produced by the methylation of histamine in the liver, was inactive. Imidazole-4-acetaldehyde, the first derivative of the oxidative deamination of histamine has not been synthesized, but the next derivative, imidazole-4-acetic acid, was inactive. Among the five histamine diamine oxidase inhibitors studied in relation to gastric secretion to date, aminoguanidine is the most ideal. It has the additional advantage of not inhibiting histidine decarboxylase.

Download Full-text