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.

Plasma diamine oxidase (DAO) activity after heparin injection, a circulatory mar­ ker for the intestinal mucosal integrity, was evaluated shortly after major abdo­ minal surgery. DAO activity was measured by high-performance liquid chroma­ tography method after 50 units/kg of heparin injection after esophagectomy in 8 patients, total gastrectomy in 16 patients, and pancreatectomy in 7 patients. Blood samples were collected before and at 2, 10, and 30 days after operation. Postheparin DAO activity at the 2nd day after operation decreased to 60% of the value before operation (p<0.05), then recovered gradually until the 30th day. The activity decreased in cases after esophagectomy and pancreatectomy (p

Phthalic anhydride (PA), used in the chemical industry, binds to proteins and causes allergic reactions. It is important to study the characteristics of antibody to PA-protein. We produced specific IgG against PA-rabbit serum albumin (RSA) by administering subcutaneous injections of PA-RSA conjugate to two rabbits. Both rabbits' sera had high titers of IgG not only to PA-RSA but also to PA-human serum albumin (HSA) and HSA. In enzyme-linked immunosorbent assay (ELISA) and ELISA HSA inhibition, specific IgG to PA-HSA revealed cross-reactivity to three other phthalyl anhydride conjugates, hexahydrophthalic anhydride (HHPA)-HSA, methylhexahydrophthalic anhydride (MHHPA)-HSA, and methyltetrahydrophthalic anhydride (MTHPA)-HSA, in both sera. Titers of IgG to HHPA-HSA, MHHPA-HSA, and MTHPA-HSA were not significantly different. On affinity chromatography, highly specific IgG to PA hapten alone was purified. In the serum not binding to PA column, specific IgG to PA-HSA was significantly less than in original serum, but levels of specific IgG to other phthalyl anhydride-HSA were unchanged. Rabbits immunized with PA-RSA produced at least two types of IgG: one is to PA hapten alone and the other may be against new antigenic determinants (NADs) on HSA.

Histamine plays an important role in the development of asthmatic symptoms. Diamine oxidase (DAO histaminase), which inactivates histamine, is located in the intestine and kidney and is released into plasma. Plasma DAO activity in asthmatic children was measured by a recently developed high performance liquid chromatographic method using histamine as the DAO substrate. Diamine oxidase activity was higher in severely asthmatic children than in those with mild asthma. A time course study during the acute exacerbation phase revealed that DAO activity rose during acute asthmatic attacks and then decreased gradually over several days. Although the mechanisms of plasma DAO activity increase during acute asthmatic attacks could not be explained, data showed that plasma DAO activity is an important index of histamine metabolism in asthmatics and may relate to some mechanisms of acute exacerbation of airway inflammation. Consequently, fluctuations in plasma DAO can be used as one of various indices of instability in management of asthma.

Histidine decarboxylase (HDC) mRNA in various rat tissues were quantitated by using a reverse transcription-polymerase chain reaction (RT-PCR) in which a mouse mRNA was used as an internal standard. The stomach HDC mRNA level was the highest followed by the brain, skin, jejunum, spleen and liver. There was no measurable HDC mRNA in the kidney. The stomach HDC activity was also the highest followed by the brain, skin, spleen, jejunum, liver and kidney. A significant correlation (r = 0.940, p < 0.0001) was observed between the HDC mRNA levels and HDC activities in these tissues. We have also examined the HDC mRNA levels in fasting rats and found that HDC mRNA levels in the stomach were reduced after the 48-hr-fasting with the decrease in HDC activities. These observations indicate that there may exist a gene regulation, at least at the basal level, for the HDC activities in the rats.

Intact and antrectomized female rats were treated with the potent proton pump inhibitor, E3810 (daily 40 mg/kg weight, s.c.) for 4 weeks. Plasma gastrin concentration and urinary excretion of N-terminal big gastrin increased until day 14 and persisted at a high level in intact rats treated with E3810, but did not increase in antrectomized rats. Urinary excretion of histamine increased progressively and reached 7 times the control value following 4 weeks of treatment with E3810 in intact rats, but not in antrectomized rats. At the termination of the treatment, the endocrine cell density in the oxyntic mucosa of intact rats had increased by 85% with increased histamine content and elevated histidine decarboxylase activity, while antrectomized rats showed a low histamine level and low histidine decarboxylase activity. Administration of gastrin-17 I (10 μg/kg weight, sc) itself caused a significant increase in urinary excretion of histamine, which was inhibited by the specific gastrin receptor antagonist, L-365,260. These results suggests that the massive urinary excretion of histamine caused by the treatment with E3810 reflects gastrin-induced mobilization of gastric histamine and that neither E3810 itself nor E3810-induced luminal pH elevation has direct effects on mobilization of oxyntic mucosal histamine.

The effect of octreotide, a potent and long-acting analogue of somatostatin, on gastrin-stimulated proliferation and function of enterochromaffin-like (ECL) cells were examined in rats. Animals were divided into four groups and each group was continuously infused with saline, octreotide alone (40 micrograms/kg per day), gastrin alone (60 nmol/kg per day), or octreotide (40 micrograms/kg per day) plus gastrin (60 nmol/kg per day) respectively for 9 days via osmotic minipumps. Gastrin induced the increase of the bromodeoxyuridine labeling index and density of oxyntic mucosal ECL cells as well as oxyntic mucosal histidine decarboxylase activity. Octreotide completely abolished the gastrin-induced increases in the labeling index and density of ECL cells and oxyntic mucosal histidine decarboxylase activity. These results indicate that octreotide inhibits gastrin-stimulated proliferation of ECL cells and histamine production by these cells.

Rat C6 astroglioma cells (C6-bH1R cells) expressing cloned bovine histamine H1 receptors were established by transfection with a vector (pEF-BOS-bH1R) which carried a 2.7-kbp EcoRI fragment of the bovine H1 receptor cDNA [Yamashita, M. et al. (1991) Proc. Natl. Acad. Sci. USA 88, 11515-11519]. The cloned bovine H1 receptor in C6-bH1R cells was characterized by three established criteria: the [3H]mepyramine binding assay, the accumulation of inositol phosphates induced by histamine, and histamine-induced elevation of intracellular Ca2+ concentration ([Ca2+]i). The accumulation of inositol phosphates induced by histamine was time- and dose-dependent. The accumulation of inositol trisphosphate was biphasic with a prompt increase to the maximal level, followed by a sustained submaximal level. The histamine-induced accumulation of inositol phosphates was suppressed by phorbol ester, but not by pertussis toxin. Results from the [3H]-mepyramine binding assay and histamine-induced elevation of [Ca2+]i were characteristic of H1 receptors. Several compounds among tricyclic antidepressants, neuroleptics, and serotonin antagonists showed affinities to the cloned bovine H1 receptor with Ki values similar to reported values. Histamine neither induced cAMP accumulation nor attenuated forskolin-induced cAMP accumulation in C6-bH1R cells. C6-bH1R cells are particularly useful for studying the H1 receptor-mediated astroglial cell functions.

Interleukin-1 beta (IL-1 beta) is the most potent inhibitor of gastric acid secretion known at present. Although histamine has been shown to be an important mediator of gastric acid secretion, the effect of IL-1 beta on gastric histamine mobilization has not been studied. In the present study, the effects of IL-1 beta on gastric acid secretion and gastric histamine mobilization were investigated in conscious rats with both gastric and vesical fistulas. IL-1 beta (5 micrograms/kg iv) significantly inhibited basal acid secretion but did not affect basal urinary histamine excretion and fundic histidine decarboxylase (HDC) activity. Gastrin-17-I (1 nmol.kg-1.h-1) caused a marked increase in acid secretion, urinary histamine secretion, and fundic HDC activity. IL-1 beta (5 micrograms/kg iv) completely inhibited gastrin-induced acid secretion and partially inhibited urinary histamine excretion and fundic HDC activity. Pretreatment with indomethacin (10 mg/kg ip) partially reversed the inhibitory effects of IL-1 beta on gastrin-stimulated fundic HDC activity and acid secretion. These findings indicate that IL-1 beta inhibits gastric histamine mobilization through both prostaglandin-dependent and prostaglandin-independent pathways. Furthermore, it is suggested that the inhibitory action of IL-1 beta on gastric acid secretion is mediated by the inhibition of gastric histamine mobilization.

Diamine oxidase (DAO) was purified to homogeneity from rat small intestine, and its biochemical and immunochemical properties were studied. DAO was suggested to be a dimer of a 92 kDa subunit, and its isoelectric point was found to be 6.0. Histamine, putrescine, N tau-methylhistamine, and cadaverine were good substrates, with Km values ranging from 9.4 to 16.0 microM. Spermine and spermidine were not substrates. Both an immunoprecipitation study and Ouchterlony's double diffusion test involving antiserum against the purified DAO showed that the immunological properties of the DAOs from rat small intestine, thymus, and placenta were identical. Among small intestinal DAOs from different species, this antibody reacted to the guinea pig enzyme as strongly as to the rat enzyme, but the reaction was much weaker to the mouse enzyme than to the rat enzyme. The DAOs from rabbit and dog small intestine, pig kidney, and human placenta showed no reactivity toward this antibody.

The rat kidney histamine N-methyltransferase was purified to homogeneity from Escherichia coli transfected with its recombinant cDNA. An antiserum to the enzyme was raised in rabbit by immunization with the purified protein. Western blot analysis of rat tissues with the antiserum revealed a band with identical mobility to that of purified enzyme in the extracts of kidney, jejunum, and brain, where the enzyme activity was detected. The antiserum cross-reacted with a 32K protein in mouse liver, brain, stomach, kidney and lung, and a 33K protein in guinea pig brain, stomach jejunum, spleen, lung, and kidney. The intensity of the staining in western blotting correlated well with the enzyme activity in all the tissues in these three species, suggesting that our antiserum is useful for quantifying histamine N-methyltransferase protein in rodent tissues.