Alterations in histamine metabolism of rat gastric mucosa following vagotomy

1. In female rats subjected to truncal vagotomy with pyloroplasty, pyloroplasty alone or sham operation, the behaviour of gastric mucosal histamine was investigated combining in vivo and in vitro methods.2. Following truncal vagotomy with pyloroplasty mucosal histamine formation, determined in vitro, increased about fivefold and histamine content was significantly elevated. The heightened histamine formation was reflected in increased excretion of histamine in the urine.3. On pentagastrin infusion, mucosal histamine formation increased about twofold following vagotomy with pyloroplasty and sevenfold in the sham-operated controls. Histamine content concomitantly fell in both groups to about the same level. These alterations were paralleled by increased excretion of histamine in the urine.4. Kinetic studies in which [(14)C]histidine was injected and the resulting urinary [(14)C]histamine determined, indicated that during the first hour of pentagastrin infusion newly formed histamine was more slowly mobilized following vagotomy with pyloroplasty than in the controls.5. In rats subjected to a pyloroplasty alone, the increase in urinary histamine on pentagastrin infusion was significantly larger than in the sham-operated controls. Kinetic studies indicated that this was due to a larger mobilization of preformed histamine.6. The changes in mucosal histamine metabolism are discussed in relation to the pattern of acid secretion following the actual surgical procedures.     

Cytoprotective activity of deboxamet: a possible interference with prostaglandin and prostacyclin metabolism in rat gastric mucosa

Deboxamet (5-methoxy-2-methyl-3-indolyl-acetohydroxamic acid) is a new synthetic drug with anti-ulcer and anti-secretory activity. The authors evaluated the ability of deboxamet to protect the rat gastric mucosa against the intensive necroses induced experimentally by absolute ethanol, NaCl (25%), HCl (0.6 N), acetylsalicylic acid plus HCl, and sodium taurocholate plus HCl. Deboxamet, as compared with pirenzepine, sulglycotide and PGE2, displayed a cytoprotective activity against these necrotizing agents. The involvement of deboxamet with prostacyclin metabolism was also investigated. In order to assess the presence of PGI2-like substances, extracts of mucosa from rats treated orally with deboxamet and sulglycotide were assayed i) on isolated rabbit mesenteric artery, ii) for hypotensive effect in anaesthetized rat, and iii) for anti-platelet activity. Deboxamet, like sulglycotide, was able to raise the availability of prostacyclins in the rat gastric mucosa, which is an important action in maintaining its cellular integrity. However, our results cannot determine whether this activity is due to an enhanced biosynthesis or a decreased degradation of prostacyclins.     

Phosphopyridoxal complexes with histamine and histidine (2) the influence of presumed complex on histidine decarboxylase activity in rat gastric mucosa

It was found that in vitro, histidine and histamine form a complex compound with pyridoxal-5′-phosphate (PLP). The purpose of the present experiments was to find whether formation of this complex can influence histidine decarboxylase activity. It was found that excess PLP inhibits rat's gastric mucosa histidine decarboxylase activity in vitro. The inhibitory action of PLP depends on the histidine concentration and is independent on the amount of crude enzyme preparation. The histidine-PLP complex did not influence enzyme activity. The possible mechanisms of the inhibitory action of PLP on histidine decarboxylase activity are discussed.     

Effect of cimetidine and carbenoxolone on cysteamine-induced ulcers: A study of gastric mucosal histamine and histamine formation capacity in rat

Cysteamine-induced ulcers in rat were used to study the effect of ulcer-healing agents with different modes of action on ulcer formation and mucosal histamine.Male Wistar rats were divided into 5 groups. Group I had cysteamine injection; group II had cimetidine followed by cysteamine injection; group III had carbenoxolone before cysteamine injection; group IV had carbenoxolone as group III and cimetidine and cysteamine injections; group V had saline injections (controls).In group I 20/29; group II 17/30; group III 15/29; and group IV 23/30 developed ulcers. No significant differences were found. No ulcers were found in group V. Comparison between all groups and controls showed an increase in gastric mucosal histamine and HFC. The increase in histamine was related to ulcer formation. Duodenal and oesophageal histamine did not change significantly. Gastric mucosal histamine and HFC were directly correlated.Neither cimetidine nor carbenoxolone alone or in combination prevent formation of ulcers following cysteamine administration. Cysteamine administration is followed by an increase in gastric mucosal histamine and HFC, which is not modified by cimetidine or carbenoxolone.     

A study of the vascular and acid-secretory responses of the rat gastric mucosa to histamine.

1. The effects of histamine on gastric mucosal blood flow in the presence and absence of gastric acid secretion were studied in the rat. 2. Histamine, in doses greater than those required to stimulate maximal acid secretion, caused a small increase in mucosal blood flow per unit acid output. 3. When acid secretion was inhibited by methyl analogues of prostaglandin E2, histamine reduced arterial blood pressure and gave a dose dependent rise in mucosal blood flow. 4. When acid secretion was inhibited by the histamine H2-receptor antagonists, burimamide and metiamide, histamine still increased mucosal blood flow. 5. The use of H1-receptor antagonists to inhibit the histamine-induced hyperaemia was made difficult by their vasodilator actions. 6. The selective histamine H2-receptor agonist, 4-methyl histamine, had no effect on arterial blood pressure in doses which stimulated acid secretion. The increase in mucosal blood flow which accompanied the stimulation of acid secretion was inhibited by the anti-secretory prostaglandins and H2-receptor antagonists. 7. The selective histamine H1-receptor agonist, 2-pyridyl ethylamine, had no effect on acid output but increased resting mucosal blood flow. 8. These results suggest that histamine H2-receptors, primarily concerned with acid secretion, and H1-receptors concerned with vasodilatation are both present in the rat gastric mucosa.     

Effect of a cholesterol-rich diet on cholesterol content and phagocytic activity of rat macrophages

Treatment for 11–13 weeks with a cholesterol-rich diet induced increases in free and esterified serum cholesterol. There was also an increase in free cholesterol of peritoneal macrophages. A 2.2 times rise in the cholesterol to phospholipid ratio of plasma membranes occurred in cholesterol-enriched macrophages. No changes were observed in phagolysosomes. Cholesterol-enriched macrophages showed a 35.8% inhibition of latex particles phagocytosis. When lipid droplets were substituted for latex the inhibition was 81.7%.     

Effect of vagotomy on ultrastructural organization of the enterochromaffin cells of the rat duodenal mucosa

An electron-microscopic study was made of the enterochromaffin cells (ECC) of the duodenal mucosa of rats 7, 14, 28, and 56 days after bilateral subdiaphragmatic vagotomy. The results indicate that vagotomy leads to considerable changes in the ultrastructural organization of the ECC, resulting in disturbance of the secretion of 5-hydroxytryptamine (serotonin). The process described is fluctuating in character. The changes reach a maximum on the 7th and 56th days after the operation, with a temporary return almost to the initial level after 28 days.Department of Histology and Embryology, Faculty of Internal Medicine, N. I. Pirogov Second Moscow Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Kupriyanov). Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 82, No. 9, pp. 1131–1133, September, 1976     

幽门螺旋杆菌对大鼠和人胃粘膜细胞株增殖的影响

本工作观察了幽门螺旋杆菌菌体超声粉碎提取物对大鼠胃粘膜细胞株ＲＧＭ１和人胃腺癌细胞株ＢＧＣ－８２３增殖的影响。结果显示Ｈｐ提取物对两种细胞增殖的影响不一：在ＲＧＭ１细胞,Ｈｐ提取物作用使ＭＴＴ比色法ＯＤ值和＾３Ｈ－ＴｄＲ掺入值明显降低,在ＢＧＣ－８２３细胞,Ｈｐ提取物作用使ＭＴＴ比色法ＯＤ值和＾３Ｈ－ＴｄＲ掺入值明显增高。表明Ｈｐ提取物抑制大鼠胃粘膜细胞株增殖而促进人胃腺癌细胞株增殖。提示细胞的状     

Effect of gastric irradiation on gastric secretion and histamine in mice

Gastric irradiation selectively inhibits acid secretion. Histamine may have a role in the inhibitory process. Seven days after gastric irradiation with 9 Gy X-rays, mice underwent a stomach perfusion and secretion test. Under pentagastrin stimulation (62.5 g/kg), acid and histamine secretion was significantly lower than that of the unirradiated controls, while pepsin and potassium outputs were unchanged. Histamine concentration in the oxyntic region of the stomach assayed after the perfusion test was significantly lower than that of controls. It is postulated that the fall in the endogenous histamine store may contribute to the reduction in acid production.     

Microelectrode determination of oxyntic cell pH in intact frog gastric mucosa. Effect of histamine

Intracellular pH (pH_i) of acid-secreting cells was measured in intact gastric fundus mucosa of Rana esculenta with double-barrelled pH microelectrodes. Tissues were mounted, serosal side up, between two half chambers and individual cells were impaled after microsurgical removal of the serosal muscle layer. Transepithelial potential difference (V _t) and resistance (R _t) as well as serosal cell membrane potential (V _s) and pH_i were continuously recorded at rest (0.1 mmol/l cimetidine) or during stimulation (0.5 mmol/l histamine). During chamber perfusion with HCO3 ₃ ^– /CO₂-buffered Ringer solution of pH_o=7.36, V _t and R _t were –21.7, SD±6.0 mV and 229±83 cm²(n=17) while V _s and pH_i averaged –7.3±6.9 mV and 7.4±0.11 (n=25). The latter value is considerably more alkaline than all recent pH_i measurements obtained with microspectrofluorometric techniques on isolated cells, glands or intact tissue. The difference may in part be explained by use of HCO ₃ ^– -free solutions in most of the previous studies because we observed that such solutions decrease pH_i to 6.89±0.18 (n=4). Again, in contrast to recent literature, application of histamine in HCO ₃ ^– /CO₂-buffered solution led to further transient alkalinization by 0.12±0.05 pH unit (n=8). Since in accidental punctures of the gastric gland lumen we noticed that H⁺ secretion only began approximately 5 min after histamine application, we conclude that the histamine-induced initial alkalinization does not reflect stimulation of the H⁺/K⁺ ATPase pump. Alternatively, it may result from histamine-induced activation or inactivation of other ion transporters, one possibility being activation of basolateral Na⁺/H⁺ and Cl^–/HCO ₃ ^– exchangers.     

Effect of amodiaquine on histamine level and histamine-methyltransferase activity in the rat brain

Amodiaquine, 10(-5) M, totally inhibited the activity of histamine-methyltransferase (HMT) in the rat brain. Both peripheral (60 mg/kg i.p.) and central (50 and 100 microgram i.vt.) administration of the drug substantially reduced the HMT activity. Amodiaquine given i.p. or i.vt., in various doses, did not change the endogenous histamine (HI) level in the rat brain at any time studied (1-24 h). Amodiaquine (60 or 120 mg/kg i.p.) administered together with an inhibitor of diamine oxidase, i.e. aminoguanidine (either peripherally or centrally) had no effect on the endogenous HI content. Possible involvement of mechanisms other than methylation or oxidation in regulation of the endogenous HI level in the rat brain is discussed.     

Inhibition of histamine biosynthesis and gastric function in the rat: effect on pentagastrin-induced gastric acid secretion

A very simple and rapid method to measure gastric acid secretion in the conscious unoperated fasted rat is reported. Antisecretory activity of cimetidine and hypersecretory activity of pentagastrin are detected by this procedure. Pentagastrin induces gastric acid secretion and causes an increase by 2-fold in histidine decarboxylase activity. There is a delay between the increase of gastric acid output and the appearance of histidine decarboxylase activity. Co-administration of monofluoromethyl histidine, a specific irreversible inhibitor of histidine decarboxylase, does not modify the peak response to pentagastrin but shortens the duration of stimulation. We suggest from this data that histamine biosynthesis is needed for maintenance of elevated gastric acid secretion.