Biomedical subjects

I Imamura

Publications and source records attributed to I Imamura.

At least 37 records · Page 2Linked to original sources

PubMed1993

Somatostatin inhibits gastrin-induced histamine secretion and synthesis in the rat.

Somatostatin is a potent inhibitor of gastric acid secretion. However, the effect of somatostatin on gastric histamine secretion and synthesis has not been well understood, despite the fact that histamine plays a key role in the regulation of gastric acid secretion. This study was designed to determine the effect of somatostatin on gastric histamine mobilization and acid secretion in conscious rats. In conscious rats with a gastric fistula, a 4 h intravenous infusion of gastrin-17 I (1 nmol/kg/h) evoked a marked increase in fundic histidine decarboxylase activity (the sole histamine-forming enzyme) and reduced fundic histamine content with a concomitant increase in gastric acid secretion. Somatostatin-14 (10 nmol/kg/h) significantly inhibited gastrin-induced gastric acid secretion and fundic histidine decarboxylase activity and prevented a gastrin-induced decrease in fundic histamine content. In conscious rats with a vesical fistula, somatostatin-14 (10 nmol/kg/h) significantly inhibited the urinary histamine excretion induced by a gastrin-17 I (1 nmol/kg/h) infusion. These findings suggest that the inhibitory action of somatostatin on gastrin-induced acid secretion is mediated by the inhibition of histamine mobilization.

Animals↗

PubMed1993

Histamine content, synthesis and degradation in human nasal mucosa.

Histamine content and enzyme activities of histamine metabolism, histidine decarboxylase (HDC), histamine N-methyltransferase (HMT) and histaminase (diamine oxidase, DAO) in human nasal mucosa were determined with a highly sensitive and specific fluorescent method which was combined with high performance liquid chromatography. Histamine content and HDC activity were determined in 10 specimens of nasal polyp, nine specimens of maxillary sinus and five specimens of inferior turbinate. HMT and histaminase activities were determined in 15 specimens of nasal polyp, nine specimens of maxillary sinus and five specimens of inferior turbinate obtained during surgical therapy. Histamine and activities of HDC, HMT and histaminase were detected in all specimens except the case of histaminase activity in one specimen of nasal polyp. The mean values of histamine content and activities of HDC, HMT and histaminase of human nasal mucosa were 137.3 nmol/g wet weight, 26.3 fmol/min/mg protein, 26.4 pmol/min/mg protein and 0.5 pmol/min/mg protein, respectively. Histamine content in the mucosal tissue of the maxillary sinuses was significantly higher than that of nasal polyps or inferior turbinates. There were no significant differences in HDC activities among three kinds of nasal mucosa. Activities of HMT and histaminase, including their kinetic constants (Km and Vmax values for histamine) indicated that HMT has a greater potential than histaminase for histamine degradation in the human nasal mucosa. The presence of these enzymes suggests that these activities constitute an important modulating factor in histamine mediated allergic and inflammatory reactions in human nasal mucosa.

Adolescent↗

PubMed1993

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

We have reported the presence of a histamine synthesizing enzyme, histidine decarboxylase (HDC), and histamine degrading enzymes, histamine N-methyltransferase (HMT) and histaminase (diamine oxidase, DAO) in human nasal mucosa and the histamine content of the mucosa. In this study, we demonstrate the influences of the toluene diisocyanate (TDI) treatment on the histamine content and these enzyme activities in guinea-pigs as an animal model of respiratory hypersensitivity. Application of TDI to the nasal vestibuli induced intense nasal allergy-like and mild asthma-like responses in TDI-sensitized guinea pigs. Increases in the histamine content and HDC and HMT activities were observed in the nasal mucosa and lung of TDI-sensitized guinea pigs. No apparent changes in the histaminase activities were observed in either the nasal mucosa or the lung. These data suggest that the turnover rate of histamine is increased in the nasal mucosa and the lung of guinea pigs with respiratory hypersensitivity.

Amine Oxidase (Copper-Containing)↗

PubMed1993

Histamine metabolism in nasal polyps.

We attempted to determine the relationship of nasal polyps to histamine (HA) metabolism. Compared to that in allergy-related nasal polyps and infection-related nasal polyps, the level of HA in aspirin-induced asthma-related polyps was significantly lower. Large differences between the groups were not observed in HA-synthesizing enzyme activity, but degradative enzyme activity was much higher in aspirin-induced asthma-related polyps than in other types of nasal polyps tested. These findings suggest the possibility that the amount of HA in polyps associated with aspirin-induced asthma was less because of greatly enhanced degradation. We found, in addition, that in nasal tissues such as polyps, histamine-N-methyl transferase, rather than histaminase, was the principal degradative enzyme.

Amine Oxidase (Copper-Containing)↗

PubMed1993

Marked increase in fundic mucosal histidine decarboxylase activity in a patient with H+,K(+)-ATPase antibody-positive autoimmune gastritis.

A 63-year-old woman was diagnosed as autoimmune gastritis by the presence of serum antibody against alpha-subunit of gastric H+,K(+)-ATPase. The patient did not have pernicious anemia, but showed achlorhydria, marked hypergastrinemia, enterochromaffin-like cell hyperplasia and an extremely high histidine decarboxylase activity in the gastric fundic mucosa. Intragastric acidification by infusion of hydrochloric acid via a nasogastric tube induced a transient reduction of serum gastrin level and fundic mucosal histidine decarboxylase activity. A marked increase in fundic mucosal histidine decarboxylase activity as well as hypergastrinemia appears to be the pathophysiologic response to achlorhydria caused by autoimmunity against gastric H+,K(+)-ATPase.

Achlorhydria↗

PubMed1993

[Comparison of gastrointestinal toxicity of 5-FU derivatives].

Gastrointestinal toxicities of tegafur (FT) and doxifluridine (DFUR) were compared using mouse intestinal enzymes as the marker. Enzyme activities were decreased during repeated administration of these 5-FU derivatives. When the drugs were administrated once a day, the decrease of enzyme activities were almost equal, but when administrated twice a day. DFUR showed greater decrease. Pharmacokinetical analysis revealed faster catabolism of DFUR than FT. In vitro 5-FU formation by GI extract was much higher from DFUR than FT. These data show a good agreement with the fact that the incidence of diarrhea is much higher in DFUR than FT.

Administration, Oral↗

PubMed1992

Re-examination of [3H]mepyramine binding assay for histamine H1 receptor using quinine.

[3H]Mepyramine, a potent antagonist of the histamine H1 receptor, has been widely used as a radioligand binding assay for the H1 receptor. Previously, we purified a mepyramine binding protein (MBP) from rat liver, but found that its partial amino acid sequences were very similar to those of debrisoquine 4-hydroxylase isozymes (P450 db1 and db2), which are members of the superfamily of cytochrome P450. Using cloned histamine H1 receptor cDNA, we found that [3H]mepyramine could bind only the H1 receptor and did not bind MBP in the presence of 10(-5) M quinine, an inhibitor of debrisoquine 4-hydroxylase isozymes. We developed a method to determine the contents of the H1 receptor and MBP separately using [3H]mepyramine and quinine and found that MBP is abundant in certain areas of bovine brain.

Animals↗

PubMed1992

Histamine N-methyltransferase from rat kidney. Cloning, nucleotide sequence, and expression in Escherichia coli cells.

Complementary DNA clones encoding rat kidney histamine N-methyltransferase have been isolated using synthetic oligonucleotide probes based on partial amino acid sequences of tryptic peptides of the purified enzyme. The 1.3-kilobase cDNA consisted of a 5'-noncoding region of 8 nucleotides, a coding region of 885 nucleotides, and a 3'-noncoding region of 369 nucleotides. The encoded protein of 295 amino acid residues had a calculated molecular weight of 33,940.2. After introduction of a prokaryotic expression vector containing the isolated cDNA, Escherichia coli cells expressed histamine N-methyltransferase activity. The enzyme expressed in these cells was isolated and purified as a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, whose mobility was identical to the natural enzyme purified from rat kidney. The recombinant enzyme had Vmax and Km values for both histamine and S-adenosylmethionine identical to those of the natural enzyme. All of the inhibitors of the natural enzyme tested showed similar Ki values on both recombinant and natural enzyme.

Amino Acid Sequence↗

PubMed1992

Zinc-deficient diet impairs adaptive changes in the remaining intestine after massive small bowel resection in the rat.

An investigation was conducted on the influence of the presence of zinc in an elemental diet on the mucosa of residual intestine after massive small bowel resection. A total of 34 male Sprague-Dawley rats were divided into five groups: control animals (n = 10) were killed after overnight fasting; a second group (n = 14) underwent massive small bowel resection preserving 10 cm of terminal ileum, and the third group (n = 10) underwent sham operation. Animals in the second and third groups were fed either a commercially available elemental diet or a zinc-deficient diet for 2 weeks; they were then killed. In animals receiving the zinc-deficient diet, a significant decrease (P < 0.05) was noted in plasma zinc and total protein, and in mucosal wet weight (duodenum), thickness (duodenum and ileum), and protein (duodenum) and DNA (duodenum) content. Mucosal sucrase and maltase specific activities in the duodenum and ileum fell but diamine oxidase levels did not. These results suggest that zinc plays an important role in intestinal adaptation in the rat, and indicate that this trace element is essential for intestinal mucosal preservation in this animal.

Adaptation, Physiological↗

PubMed1992

Histamine and histidine decarboxylase are correlated with mucosal repair in rat small intestine after ischemia-reperfusion.

The aim of this experiment was to demonstrate whether histamine and histidine decarboxylase (HDC) contribute to mucosal repair in small intestine subjected to ischemia-reperfusion (I/R). The superior mesenteric artery was occluded for 15 min followed by reperfusion. In jejunal mucosa, histamine content and HDC activity increased after I/R. Histamine output in mesenteric lymph was also elevated after I/R. These increases in HDC activity, and mucosal and lymph histamine levels were suppressed by pretreatment of alpha-fluoromethylhistidine (alpha-FMH), a suicide inhibitor of HDC. alpha-FMH also attenuated the increase of ornithine decarboxylase (ODC) activity normally observed after I/R. Transport of dietary lipid into lymph markedly decreased at 24 h after I/R, yet it was restored to normal at 48 h after I/R. alpha-FMH inhibitor led to a sustained deficit in lipid transport at 48 h after I/R. This sustained functional impairment in alpha-FMH treated animals was associated with blunted responses of HDC activity and histamine content to I/R. Our results suggest that histamine and HDC contribute to the restoration in mucosal function observed at 48 h after I/R. This response may be related, at least in part, to stimulation of ODC activity by histamine.

Amine Oxidase (Copper-Containing)↗

PubMed1992

Effects of capsaicin desensitization on nasal allergy-like symptoms and histamine release in the nose induced by toluene diisocyanate in guinea pigs.

Intranasal application of toluene diisocyanate (TDI) induced nasal allergy-like symptoms of sneezing and watery rhinorrhea and decreased the histamine content of the nasal mucosa in guinea pigs. However, in the animals pretreated with capsaicin (capsaicin desensitization) before sensitization with TDI, nasal allergy-like symptoms were not induced. Capsaicin desensitization also inhibited histamine release in the nasal mucosa induced by TDI. These findings suggest that antidromic impulses of capsaicin-sensitive sensory nerves stimulated by TDI cause histamine release from mast cells in the nasal mucosa, resulting in nasal discharge and sneezing in guinea pigs. Thus neurogenic inflammation via an axon reflex in the nose may contribute to the pathogenesis of vasomotor rhinitis.

Animals↗

PubMed1991

Effect of cholecystokinin receptor antagonists, MK-329 and L-365,260, on cholecystokinin-induced acid secretion and histidine decarboxylase activity in the rat.

To elucidate the regulatory mechanism of acid secretion by cholecystokinin (CCK) in vivo, we compared the effects of CCK and gastrin on acid secretion and histidine decarboxylase (HDC) activity. We also examined the effects of MK-329, a specific antagonist for pancreatic-type CCK receptor, and L-365,260, a specific antagonist for gastrin-type CCK receptor, on the action of CCK. Graded doses of CCK or gastrin were intravenously infused into conscious rats with gastric fistula. Gastrin-17 I infusion up to 10 nmol/kg/h resulted in dose-related increases in acid secretion. CCK-8 infusion also caused an increase in acid secretion. However, it reached a peak with 0.3 nmol/kg/h CCK-8 and attenuated with higher concentrations of CCK-8. This attenuating effect of a higher dose of CCK was reversed by MK-329, but not by L-365,260. Both CCK and gastrin were potent in increasing fundic HDC activity, and the effect of CCK on HDC activity was significantly inhibited by L-365,260, but not by MK-329. Taken together, the present study suggests that CCK and gastrin stimulate histamine formation via a gastrin-type CCK receptor, and the attenuating action of CCK with higher concentrations on acid secretion in vivo is mediated by a pancreatic-type CCK receptor.

Animals↗

PubMed1991

High-performance liquid chromatographic determination of histamine N-methyltransferase activity.

A method for the determination of histamine N-methyltransferase (HMT) activity by high-performance liquid chromatography based on post-column derivatization with omicron-phthalaldehyde is described. The determination involves the separation of the substrate, histamine, from its product. N tau-methylhistamine, using a weak cation exchanger, followed by on-line derivatization of these imidazoleamines with omicron-phthalaldehyde and their detection and quantitation with a fluorimetric detector. This assay method is suitable for the measurement of HMT activity during enzyme purification.

Animals↗

PubMed1991

Marked increase in gastric histidine decarboxylase activity in patients with hypergastrinemia.

Histidine decarboxylase (HDC) activity and histamine content were measured in endoscopic gastric biopsy specimens of 19 control subjects with normogastrinemia and 6 patients with hypergastrinemia. In controls, the HDC activity was 3 fold higher in fundic mucosa (120 +/- 13 fmol/min/mg protein, mean +/- S.E.) than in antral mucosa (39 +/- 5 fmol/min/mg protein). In patients with hypergastrinemia, an extremely high HDC activity (713 +/- 181 fmol/min/mg protein) was observed in fundic mucosa, although the HDC activity in antral mucosa was not significantly different from that of controls. The histamine content in fundic mucosa was also significantly higher in patients with hypergastrinemia than in controls but no significant difference was seen in histamine content in antral mucosa between the two groups. These results are compatible with the hypothesis that in man, as well as in rat, histamine synthesis in fundic mucosa is enhanced by gastrin.

Adult↗

PubMed1991

High efficacy of monomethoxypolyethylene glycol-conjugated L-asparaginase (PEG2-ASP) in two patients with hematological malignancies.

Two patients with hematological malignancies were successfully treated with monomethoxypolyethylene glycol-conjugated Escherichia coli L-asparaginase (PEG2-ASP), which reportedly lacks both antigenicity and immunogenicity but retains catalytic activity as well as slow clearance in an experimental animal model. A 20-year-old male patient with leukemic lymphoma was refractory to conventional chemotherapy but responsive to L-asparaginase (L-ASP) followed, however, by severe adverse effects. On relapse, an intravenous infusion of 100-200 IU/day dose of PEG2-ASP alone led to a complete remission 2 months later without hypersensitivity or other significant adverse reactions. Surprisingly, he remained in a complete remission for over one year with a regular weekly infusion of PEG2-ASP, combined with a weekly small dose of Ara-C. During this period, blood asparagine was not detectable. The other patient, a 64-year-old woman with chronic myelogenous leukemia in blast crisis achieved, within 6 weeks, a complete remission with twice-weekly infusions of PEG2-ASP. Thus, PEG2-ASP is a highly effective antitumor agent overcoming the limitations in therapeutic use of L-ASP.

Adult↗

PubMed1991

Organ assimilation of peptides.

Dipeptides injected intravenously or added to liver perfusion medium were hydrolyzed rapidly to amino acids. The clearance volumes per min of plasma Gly-Phe and Gly-Lys were 63% and 224%, respectively, of the total plasma volume. These values far exceed the blood flow in any single organ, suggesting that several organs must be involved in peptide assimilation. Intravenous administration of peptides increased the levels of their constituent amino acids in organs. Two possible explanations for this were assimilation of the peptides by the organs, and transport into the organs of the amino acids generated by extracellular hydrolysis of the peptides. The former possibility was tested by eliminating plasma lysine by enzymic degradation, so that the amino acid would accumulate only in the organs that assimilate lysine-containing peptides. Results showed that all organs tested, except the brain, had an intrinsic ability to assimilate peptides.

Animals↗

PubMed1991

[Histamine metabolism in the nasal tissue of human and nasal hypersensitive guinea-pig].

Histamine (HA) is the most important mediator of nasal allergy and nasal hypersensitivity. To investigate HA metabolism, HA content and activities of its synthetic enzyme, histidine decarboxylase (HDC) and degrading enzymes, histamine-N-methyltransferase (HMT) and diamine oxidase (DAO) in nasal mucosa of human and toluene diisocyanate (TDI) sensitized guinea-pigs were measured. In human nasal mucosa and nasal polyps, HA content and HDC activity were 80-200 nmol/g tissue, 20-30 fmol/min/mg protein respectively. Among two degrading enzymes, HMT activity was 20-200 times higher than that of DAO. In the nasal mucosa of guinea-pigs, HA content was significantly increased by TDI sensitization, and was decreased immediately after TDI provocation. In 24 hours after provocation, HA content recovered to 80% of pre-provocation level. HDC activity increased by TDI sensitization significantly. Though HMT activity increased slightly by TDI sensitization and provocation, DAO activity was unchanged. The data suggest that, increase in turnover rate of HA is present in allergic nasal mucosa.

Amine Oxidase (Copper-Containing)↗

PubMed1991

Histamine and its synthesis in mammalian retinas.

Histamine (HA) content and histidine decarboxylase (HDC) activity were studied in the sensory retinas of the rat, guinea-pig, rabbit, dog, monkey, bovine and pig. Using a highly sensitive and specific method developed for the determination of histamine using high-performance liquid chromatography, HA was detected in the retinas of all species examined. HA content ranged from 11 (bovine) to 540 pmole/g wet tissue (dog), and HDC activity ranged from 2 (rabbit) to 150 (dog) fmol HA synthesized/min/mg protein. With the exception of the dogs, the retinal values were one order lower than those in the brain in all species examined. The canine retinas had the high HA and HDC values among the species examined, and were approximately equal to those in the brain. However, the ratios of HDC activity to HA content ranged from 0.04/min to 0.51/min. These values resembled those in the brain and were much higher than those in mast cells. This suggests that histamine in the retinas exists mainly in the neurons even though the actual amounts are small and may be involved in the physiological and the pathological responses in mammalian retinas.

Animals↗