High Concentrations Of Histamine Research Articles

Histamine Formation During Salting of Spanish Mackerel (Scomberomorus commerson)

The fresh gutted Spanish mackerel were used as raw material for salting by using ratios of fish to salt as follows: 1:1, 2:1 and 3:1 by weight. Histamine content, salt content, moisture, pH, water activity (Aw), total viable count (TVC) and histamine forming bacteria (HFB) were determined at 0, 2, 6, 7, 10 and 13 days after the salting process. The salt content increased to 19% on the 13th day and became steady through the process in all treatments. There was no significant difference in the salt content among treatments. Moisture and Aw changed inversely to salt content. The pH of all samples were 5.9-6.3 during salting. However, the histamine increased from 1.87 mg/100 g to 115.52, 158.28 and 125.10 mg/100 g on the 6th day of salting in samples with a fish to salt ratio of 1:1, 2:1 and 3:1, respectively. After 6 days, it decreased markedly in all samples until the end of the process. The highest number of TVC and HFB at both 20°C and 37°C were observed in the samples with the highest histamine content on the 6th day of salting and then decreased until the end.

Study of Histamine Effects on Phagocytosis and Enzyme Secretion of Tetrahymena Pyriformis

1. The biogenic amine histamine develops effects not only in mammalian cells and tissues but in ciliated unicellular Tetrahymena as well. In addition to binding and internalization of labelled histamine, low concentrations can stimulate the phagocytosis of cells in inorganic salt solution. 2. In inorganic solution Tetrahymena cells secrete acid hydrolases to the medium. High concentration of histamine (10 mM) decreases the secretion of three investigated acid hydrolases in a different manner. We think that in this process the primary determinant is the alkaline character of histamine. 3. The effect of histamine on phagocytosis differs from the effect on secretion since the low, physiological concentration of histamine stimulates phagocytosis, the higher concentrations inhibit it. In the background of these effects possibly the hormone character is dominant. It is supported by the fact that histamine antagonists influence the process differently.

High concentrations of histamine stimulate equine polymorphonuclear neutrophils to produce reactive oxygen species

Because high concentrations of histamine are locally released in inflammation, we investigated the effects of supraphysiological doses of histamine on the production of reactive oxygen species (ROS) by neutrophils. Isolated equine neutrophils were activated by 10(-4) to 5 x 10(-3) M histamine. The production of ROS and free radicals was estimated by luminol-enhanced chemiluminescence (CL) and electron spin resonance (ESR) with spin trapping technique. In this model of histamine-stimulated neutrophils, we tested the antagonists of H1 and H2 histamine receptors, the role of Ca2+ and Mg2+, the role of staurosporine and pertussis toxin (inhibitors of protein kinase C and proteins G) and the effects of superoxide dismutase, catalase, hydroxyl radical scavengers (phenylalanine and mannitol) and N(G)-monomethyl-L-arginine (L-NMMA), inhibitor of NO-synthase. Histamine (from 10(-5) to 10(-3) M) stimulated neutrophils to produce CL and ESR signals characterized by spin adducts of superoxide anion and/or hydroxyl radicals. The CL response was inhibited by 10(-4) and 10(-3) M H1 receptor antagonists (promethazine, pyrilamine, and diphenhydramine), by Ca2+ and Mg2+ depletion and by 10 nmoles staurosporine. CL was partially inhibited by pertussis toxin (4 microg/ mL). The ESR signals were practically suppressed by pyrilamine (an H1 receptor antagonist) and superoxide dismutase, and partially inhibited by catalase, hydroxyl radical scavengers and L-NMMA (respectively 59, +/- 30% and 68% inhibition). High concentrations of histamine stimulated the neutrophils to product ROS and free radicals via H1 receptors and the NADPH-oxidase pathway.

Biogenic amines in foods: histamine and food processing.

Biogenic amines, e.g. histamine, occur in many different foods. At high concentrations, they are risk factors for food intoxication, whereas moderate levels may lead to food intolerance. Sensitive persons, with insufficient diamine oxidase activity, suffer from numerous undesirable reactions after intake of histamine containing foods. Besides spoiled foodstuffs, especially fermented foods tend to contain elevated levels of biogenic amines, although their concentrations vary extensively not only between different food varieties but also within the varieties themselves. High histamine content in foods and beverages result from microbial contamination. The evidence of enteral histaminosis represents a challenge for the food industry to produce foods with histamine levels as low as possible. We therefore investigated critical steps for histamine formation during food production processes, and established production methods that include low-histamine technology.

Terfenadine induces toxicity in cultured cerebellar neurons: a role for glutamate receptors.

Exposure of cultured cerebellar neurons to the histamine H1 receptor antagonist terfenadine resulted in neuronal degeneration and death. Terfenadine neurotoxicity was dependent upon concentration and time of exposure. After 2 h exposure, 20 microM terfenadine reduced the number of surviving neurons by 75%, and as low as 10 nM terfenadine induced significant neurotoxicity after 5 days of exposure. Neuronal sensitivity to terfenadine changed with age in culture, and at 25 days in culture neurons appeared to be much less sensitive than at 5 or 9-17 days in culture. Neurotoxicity by terfenadine could not be prevented by high concentrations of histamine (5 mM), but it was significantly delayed by blocking NMDA or non-NMDA glutamate receptors with MK-801 or CNQX respectively, suggesting the involvement of excitatory transmission mediated by glutamate in the neurotoxicity induced by terfenadine in these neurons. We also found that the presence of terfenadine (5 microM) unveiled the potential excitotoxity of the non-NMDA receptor agonist AMPA (100 microM), and reduced the concentration of glutamate necessary to induce excitotoxicity, compared to untreated cultures. These results suggest a role for terfenadine in the modulation of the excitotoxic response mediated in cerebellar neurons through ionotropic glutamate receptors.

Placental mast cells (MC) and histamine (HA) in pregnancy complicated by diabetes class C - relation to the development of villous microvessels

The role of histamine (HA) and other mast cells (MC) mediators in local placental angiogenesis is still under consideration. In human placentae obtained after normal and complicated pregnancies MC distribution, MC numbers and HA concentrations are different. Altered vascularization in diabetes is strictly related to the severity of metabolic disorders. The White class C of diabetes in pregnancy is the last stage without recognized vascular changes. The aim of the study was to find the correlation between MC number, HA concentration and density of the network of placental vessels in diabetes White class C. Nine diabetic placentas and 9 controls were examined. HA concentration in placental samples was estimated fluorimetrically. MC in sections were marked both by tryptase/chymase antibodies and stained with toluidine blue or alcian blue. In light microscopy, using computed morphometry for quantitative analysis, the development of villous microvessels was measured in calibrated areas of the placental sections. Vascular/extravascular tissular index (V/EVTI) was calculated. The results showed that in diabetes White class C increased density of the villous network of vessels (V/EVTI: 0.33±0.027 vs 0.26±0.031 in control) correlates with higher HA concentration (365.1±36.2 ng/g of wet weight vs 251.7±22.1 ng/g of wet weight in control) and increased number of MC (5134 vs 3726 in control).

Selective Histamine Uptake Rescues Photo- and Mechanoreceptor Function of Histidine Decarboxylase-DeficientDrosophilaMutant

In insects, histamine is found both in the peripheral nervous system (PNS) and in the CNS and is known to function as a fast neurotransmitter in photoreceptors that have been shown to express selectively the hdc gene. This gene codes for histidine decarboxylase (HDC), the enzyme for histamine synthesis. Fast neurotransmission requires the efficient removal of the transmitter from the synaptic cleft. Here we identify in Drosophila photo- and mechanoreceptors a histamine uptake mechanism that can restore the function of these receptors in mutants unable to synthesize histamine. When apparent null mutants for the hdc gene imbibe aqueous histamine solution or are genetically "rescued" by a transgene ubiquitously expressing histidine decarboxylase under heat-shock control, sufficient amounts of histamine selectively accumulate in photo- and mechanoreceptors to generate near-normal electrical responses in second-order visual interneurons and qualitatively to restore wild-type visual and mechanosensory behavior. This strongly supports the proposal that histamine functions as a fast neurotransmitter also in a certain class of mechanoreceptors. A set of CNS-intrinsic neurons that in the wild type contain high concentrations of histamine apparently lacks this uptake mechanism. We therefore speculate that histamine of intrinsic neurons may function as a neuromodulator rather than as a fast transmitter.

Distribution of histamine in laying hen ovary.

In a laying hen, histamine was found to be present in all compartments of the ovary, i.e. stroma with follicles < 1 mm, small white (1-4 mm), large white (4-8 mm), atretic white, yellow preovulatory (8-35 mm) and postovulatory follicles. Stroma containing non-yolky follicles exhibited the highest histamine concentration (6080 +/- 331 ng/g wet wt. tissue) which differed significantly (P < 0.01) from histamine levels observed in all examined classes of ovarian follicles. High histamine concentration was found in small, large and atretic white follicles as well as in older postovulatory follicles whereas low levels of histamine contained yellow preovulatory and younger postovulatory follicles. Population of yolky white follicles presented significant (P < 0.01) differences in histamine level among small (4280 +/- 333), atretic (2940 +/- 193) and large (2010 +/- 110 ng/g) follicles. Within hierarchy of yellow preovulatory (F7-F1) follicles initial decrease in histamine concentration, from 859.3 +/- 51.5 ng/g in F7 follicle to 363.9 +/- 28.3 ng/g in F4 follicle, was followed by the increase as follicle matured, reaching the highest level in F1 follicle (711.4 +/- 35.9 ng/g). In postovulatory (P1-P5) follicles histamine concentration gradually increased as they were getting older, from 604.3 +/- 49.3 ng/g in P1 follicle to 2253 +/- 197 ng/g in P5 follicle. Determination of histamine in relation to ovulation revealed significant (P < 0.01) difference both in histamine concentration and content between the largest preovulatory F1 follicle and the largest postovulatory P1 follicle, being 0.5 h before and 0.5 h after ovulation, respectively. It is suggested that in chicken, ovarian histamine may play a role in the follicular development and/or the ovulatory process.

Long-term increase of hippocampal excitability by histamine and cyclic AMP

The action of histamine (HA) on rat hippocampal CA1 pyramidal cells in vitro was investigated in slices perfused with solution containing 0.2 mM Ca 2+ 4.0 mM Mg 2+ . Extracellular recordings of the spontaneous discharges occurring under these conditions revealed that HA caused a long-lasting increase in cell firing. The HA-effects were dose-dependent, in that low concentrations of HA (0.1–0.5 μM) exhibited an initial transient depression of cell firing and practically no long-lasting action, whereas higher concentrations of HA (1–10 μM) exerted strong, non-declining increases. The H 1-receptor antagonist mepyramine (1 μM) blocked the initial depression of firing and attenuated the long-lasting HA-mediated excitation. Pure H 1-receptor activation, tested with the H 1-receptor agonist 2-(3-fluorphenyl)histamine (1–10 μM) depressed cell firing, similar to the low dose effects of HA. HA-induced excitations were prevented by the H 2-receptor antagonist cimetidine (10–50 μM), and mimicked by the very potent H 2-receptor agonist impromidine (1 or 3 μM) which was, however, less effective compared to equal concentrations of HA. H 3-receptor activation by R-α-methylhistamine had no significant effect on cell firing. Thus, histamine H 1 and H 2 receptors seem to cooperate in producing this long-lasting augmentation of excitability. 8-Bromo-cyclic AMP monophosphate (8-Br-cAMP, 50–100 μM) mimicked the long-term excitation, whereas the adenylyl-cyclase inhibitor 9-tetrahydro-2-furyladenine (THFA, 100–500 μM) or the PKA-inhibitor Rp-adenosine-3′5′-cyclic monophosphate (Rp-cAMPS, 10 μM) blocked it, indicating that the HA-mediated increase of excitability in the hippocampus is dependent on the adenylate cyclase/PKA-signal transduction cascade. dl-2-Amino-5-phosphonopentanoic acid (APV, 50 μM) significantly attenuated the magnitude of the HA-induced enhancement, indicating an NMDA receptor-dependent component. Other biogenic amines, acting through receptors positively coupled to adenylyl cyclase, elicited similar responses as HA, indicating common mechanisms by which these substances modulate excitability in CA1 pyramidal cells.

Histamine mediates the muscle layer-specific responses in the isolated swine myometrium.

To clarify the role of histamine in uterine contractility, the effect of this biogenic amine on the myometrium of cyclic mature gilts was investigated by an isometric tension recording study in vitro. In addition, using crude membrane preparations isolated from the longitudinal (LM) and circular muscle (CM), the distribution of H1 histamine receptors was characterized by 3H-pyrilamine binding assay. Histamine caused a tetrodotoxin-resistant contractile response of LM and CM in Krebs solution, but LM (-logEC50 = 6.34) was more sensitive than CM (-logEC50 = 5.4). Pyrilamine decreased the excitatory response of histamine in both muscle layers. In pyrilamine-treated LM, a high concentration of histamine (1-30 microM) caused a slight inhibition of spontaneous contraction, and this inhibition was abolished by ranitidine. On the other hand, histamine did not cause any inhibition in the pyrilamine-treated CM preparations. Dimaprit (10-300 microM) concentration-dependently inhibited the spontaneous contraction of LM but not of CM. In the presence of pyrilamine and ranitidine, N alpha-methylhistamine, even at 10 microM, did not affect the spontaneous and electrical field stimulation (5Hz)-induced contraction of LM and CM layers. Specific 3H-pyrilamine binding sites were distributed heterogeneously in the swine myometrium. The maximum number of binding sites in LM (132.5 +/- 9.9 fmol/mg protein, n = 10) was 2.5 times higher than that in CM (52.2 +/- 3.2 fmol/mg protein, n = 6). These results indicate that there is a muscle layer-dependent difference of histamine-induced response in the swine myometrium. In the LM layer, histamine acts on both H1 and H2 histamine receptors, and causes contraction (via H1 receptors at a low concentration) or relaxation (via H2 receptors at a high concentration in the presence of pyrilamine). However, histamine causes only a contraction in the CM layer, likely the result of the absence of H2 histamine receptors. Histamine-induced contraction is conspicuous in the LM layer, because of the heterogeneous distribution of H1-receptors between LM and CM.

Histamine content in colorectal cancer. Are there sufficient levels of histamine to affect lymphocyte function?

Histamine has been found to stimulate growth of colorectal cancer in vitro and in vivo. Histamine has also been found to inhibit lymphocyte activity in vitro at concentrations greater than 10(-7) M. The aim of our study was to determine if the histamine concentrations in human colorectal cancer were sufficient to achieve these effects. We measured the histamine content in 31 colorectal cancer specimens using a radioenzymatic assay. Results were expressed as microgram histamine per gram of fresh tissue weight. Recovery and reproducibility studies were also carried out. The median histamine concentration in colorectal cancer tissue was 8.4 micrograms/g [7.6 x 10(-5)M], ranging from 0.3 microgram/g to 20.6 micrograms/g. The high concentration of histamine in colon cancer is enough to be locally immunosuppressive.

Influence of pasteurised milk, raw milk and different ripening cultures on biogenic amine concentrations in semi-soft cheeses during ripening

In semi-soft cheeses, produced with pasteurised milk, raw milk and different starter cultures, the concentrations of cadaverine, histamine, phenylethylamine, putrescine and tyramine were investigated. The cultures (pasteurised milk cultures, raw milk cultures and starter cultures) strongly influenced the biogenic amine concentrations in the cheeses ripened for 5 months. Two cheeses made with identical pasteurised milk, but different ripening cultures, differed greatly in their total biogenic amine concentrations (51 vs 371 mg/kg). In general, the biogenic amine concentrations increased markedly between month 2 and month 3 of cheese ripening. The high content of enterococci and Enterobacteriaceae yielded the biogenic amine concentrations. In contrast, Lactobacilli did not seem to be important. However, unspecified bacteria have to be considered, since cheeses with comparable microbiological profiles differed enormously in their biogenic amine concentrations. Semi-soft cheeses produced from pasteurised milk showed remarkably lower total biogenic amine concentrations compared to semi-soft cheeses produced from raw milk (51–1096 mg/kg vs 1011–3133 mg/kg, depending also on the ripening cultures). The highest total biogenic amine concentration (4817 mg/kg) was detected in a cheese produced from raw milk that had been stored for 36 h. In this cheese, the concentrations of cadaverine, phenylethylamine, putrescine and tyramine were higher than in all other cheeses. The highest histamine concentration was found to be in another raw milk cheese (573 mg/kg).

Membrane currents evoked by histamine in rabbit basilar artery

The membrane current evoked by histamine in isolated smooth muscle cells from rabbit basilar artery was investigated using the perforated-patch technique. When 10 microM histamine was applied in the bath at a holding potential of -60 mV, an inward current (79.2 +/- 55.8 pA) was transiently activated. An outward current was additionally evoked by 10 microM histamine when the membrane was held at -40 mV or less negative potentials. The outward but not the inward current was completely blocked by 100 nM charybdotoxin. A higher concentration of histamine (30 microM) failed to produce the inward current (3.4 +/- 4.8 pA) when Cl- concentration in the pipette was reduced. The apparent reversal potential of the inward current induced by histamine in physiological salt solution, in high-tetraethylammonium (TEA+) solution (bath), or in low-Cl- solution (pipette) was -6.3 +/- 4.4, -7.5 +/- 4.9, or -45.8 +/- 8.5 mV, respectively. Niflumic acid (100 microM) reversibly blocked the inward current, which was also blocked by 10 microM pyrilamine but not by 10 microM cimetidine. When histamine was continuously applied in the bath, spontaneous transient inward currents were generated. Removal of external Ca2+ or addition of 1 microM nicardipine or 2 mM caffeine reduced the amplitude of the histamine-induced inward current. These results suggest that histamine induces an inward current via H1 receptors at the resting membrane potential, possibly due to activation of Cl- currents. The Cl- inward current might be generated by elevation of intracellular Ca2+ via histamine receptors. The inward current may also contribute to control of the Ca2+ influx via a change in the membrane potential.

Characterization of the effects of histamine in porcine tracheobronchial lymph vessels.

We characterized the responses of lymphatic vascular smooth muscle to histaminergic-receptor stimulation and blockade and explored the mechanisms underlying the histamine-stimulated release of endothelium-derived relaxing factor (EDRF). Fresh porcine tracheobronchial lymph vessel rings mounted in organ baths were stimulated by the cumulative addition of histamine or H1, H2, and H3 receptor-specific agonists in the presence or absence of receptor-specific antagonists. Histamine had a contractile effect on lymphatic vascular smooth muscle that was H1 receptor mediated. No important effects were elicited by H2- or H3-receptor stimulation. Histamine also caused the release of EDRF as demonstrated by an increase in smooth muscle tone in the absence of endothelium and after inhibition of nitric oxide synthase. This effect was strong at high concentrations of histamine and was mediated by H1-receptor stimulation. The results suggest that histamine may contribute to the regulation of lymphatic vascular smooth muscle tone under pathological conditions, an effect that may be controlled through modification of H1-receptor activity.

Widespread distribution of histamine in the nervous system of a trematode flatworm.

In general, most flatworms contain very little histamine (HA) and their nervous systems often lack, or contain very few, histaminergic elements. However, preliminary studies in our laboratory have revealed that the frog lung parasite, Haplometra cylindracea (Trematoda: Digenea), contains HA in a very high concentration. For this reason, the present study was undertaken to study the localization and synthesis of HA in this worm by using immunocytochemistry and high-pressure liquid chromatography (HPLC). Essentially all parts of the nervous system of H. cylindracea showed HA-like immunoreactivity. The paired cerebral ganglia and nerves emanating from these, including the longitudinal nerve cords, were intensely immunoreactive. The musculature of the pharynx, oral and ventral suckers, and those of the reproductive organs were all innervated by HA-immunoreactive fibers. Fiber plexuses beneath the tegument and throughout the parenchyma also showed HA-like immunoreactivity. HPLC studies revealed one of the highest HA concentrations in the animal kingdom, 6.49 +/- 1.36 nmole/mg protein, in the worm. The frog lung and blood contained very low concentrations of HA and could be excluded as sources for HA, while an enzyme assay revealed that the worm produces HA by decarboxylation of histidine. Thus, it is likely that H. cylindracea uses HA as a neurotransmitter or modulator.

Widespread distribution of histamine in the nervous system of a trematode flatworm

In general, most flatworms contain very little histamine (HA) and their nervous systems often lack, or contain very few, histaminergic elements. However, preliminary studies in our laboratory have revealed that the frog lung parasite, Haplometra cylindracea (Trematoda: Digenea), contains HA in a very high concentration. For this reason, the present study was undertaken to study the localization and synthesis of HA in this worm by using immunocytochemistry and high-pressure liquid chromatography (HPLC). Essentially all parts of the nervous system of H. cylindracea showed HA-like immunoreactivity. The paired cerebral ganglia and nerves emanating from these, including the longitudinal nerve cords, were intensely immunoreactive. The musculature of the pharynx, oral and ventral suckers, and those of the reproductive organs were all innervated by HA-immunoreactive fibers. Fiber plexuses beneath the tegument and throughout the parenchyma also showed HA-like immunoreactivity. HPLC studies revealed one of the highest HA concentrations in the animal kingdom, 6.49 ± 1.36 nmole/mg protein, in the worm. The frog lung and blood contained very low concentrations of HA and could be excluded as sources for HA, while an enzyme assay revealed that the worm produces HA by decarboxylation of histidine. Thus, it is likely that H. cylindracea uses HA as a neurotransmitter or modulator. © 1996 Wiley-Liss, Inc.

H1-receptor-mediated excitation and facilitation of the heat response by histamine in canine visceral polymodal receptors studied in vitro.

1. We examined excitation and the facilitatory effect on the heat responses induced by histamine in visceral polymodal receptors with the use of the canine testis-spermatic nerve preparation in vitro. 2. The proportion of units that showed excitation (> 10 impulses 1 min after application of histamine was initiated) increased roughly with higher concentrations of histamine: 7% at 1 microM, 26% at 10 microM, 79% at 100 microM, and 61% at 1,000 microM. The discharge rate also increased with the concentration. 3. Histamine (100 and 1,000 microM) responses > 0.5 imp/s were observed only in units with conduction velocities (CVs) of < or = 10 m/s, but not in those with CVs faster than 10 m/s. On average, histamine-induced discharges were significantly greater in units with CVs of < or = 10 m/s at all concentrations > or = 10 microM. Thus units studied in this experiment were empirically divided into slow-CV (< or = m/s) and fast-CV (> 10 m/s) groups. 4. Histamine significantly facilitated the heat responses of the slow-CV group from 10 microM, and also facilitated the fast-CV group from 100 microM. This sensitizing effect was observed irrespective of the precedent histamine-induced excitation. The magnitude of sensitization tended to increase with an increase in histamine concentration. 5. For studying the histamine receptor subtype involved in excitation and facilitation, we used D-chlorpheniramine maleate (5 microM) (an H1 receptor antagonist), famotidine (20 microM) (an H2 receptor antagonist), and thioperamide maleate (20 microM) (an H3 receptor antagonist). The magnitude of histamine-induced excitation of the slow-CV group was significantly suppressed by the H1 receptor antagonist but not by other antagonists. 6. The facilitatory effect of histamine on the heat response was also suppressed by the H1 receptor antagonist in both slow- and fast-CV groups. 7. These results strongly suggested that both excitation and facilitation of the heat response induced by histamine are mediated through the H1 receptor.

Focal [Ca2+]i increases detected by aequorin but not by fura-2 in histamine- and caffeine-stimulated swine carotid artery.

1. We hypothesized that the homogeneity of intracellular [Ca2+] ([Ca2+]i) varies and is regulated in arterial smooth muscle. 2. We evaluated this hypothesis by exploiting the different characteristics of several [Ca2+]i indicators: (1) aequorin, which theoretically can measure focal increases in [Ca2+]i, (2) fura-2, which is predominantly a measure of mean cytoplasmic [Ca2+], and (3) myosin light chain phosphorylation and force, which reflect increases in [Ca2+] near the contractile apparatus. 3. From the differences in the observed aequorin and fura-2 signals, we developed an index of the relative degree of [Ca2+]i homogeneity as the ratio of the aequorin signal and fura-2 signal. 4. Stimulation with intermediate concentrations of histamine (1 and 10 microM) or high [K+]o (25 and 40 mM) increased [Ca2+]i and contractile stress. Relative [Ca2+]i homogeneity, estimated from the aequorin/fura-2 ratio, remained similar to levels observed in unstimulated tissues. 5. Higher concentrations of histamine (100 microM) also increased [Ca2+]i and stress, but the aequorin/fura 2 ratio declined , indicating increased [Ca2+]i homogeneity. Similarly, the aequorin/fura-2 ratio decreased when extracellular Ca2+ was removed. 6. Stimulation with histamine in low extracellular [Ca2+] transiently increased [Ca2+]i and the aequorin/fura-2 ratio. Similarly, in tissues treated with low extracellular [Ca2+], restoration of extracellular Ca2+ transiently increased both [Ca2+]i and the aequorin/fura-2 ratio. Although both of these experiments demonstrated a transient decrease in [Ca2+]i homogeneity, only histamine stimulation led to increased myosin light chain phosphorylation and force. These results indicate that the focal increases in [Ca2+]i observed with histamine stimulation and Ca2+ restoration occurred in different cellular regions. 7. Addition of caffeine (20 mM) increased [Ca2+]i and [cAMP], but this was not accompanied by sustained increased myosin light chain phosphorylation or contraction. Phosphorylation of myosin light chain kinase did not appear to underlie the lack of increase in myosin light chain phosphorylation. Rather, caffeine induced a sustained increase in the aequorin/fura-2 ratio, suggesting that caffeine inhibits smooth muscle contraction by localizing increases in [Ca2+]i to a region distant from the contractile apparatus. 8. These data suggest that there can be transient and sustained focal increases in [Ca2+]i. Aequorin detected increased [Ca2+]i in small regions of the cytoplasm during release from and refilling of the intracellular Ca2+ store and with caffeine stimulation. Dual use of aequorin and fura-2 permits determination of relative [Ca2+]i homogeneity in smooth muscle.

Biogenic Amines in the Flesh of Sailfish (Istiophorus plafypferus) Responsible for Scornbroid Poisoning

ABSTRACTSailfish fillets were involved in a 1994 food poisoning outbreak in westem Taiwan. Samples were collected from the victims’residues and from retail and wholesale suppliers. They were analyzed for amines by a gradient elution system of HPLC. Tryptamine, histamine, spermine, trimethylamine, spermidine, and cadaverine were found; other amines were not detectable. The concentration of histamine was higher than 100 mg/100g which was assumed as the toxic level. The allergy‐like symptoms of the victims along with the high content of histamine in the sailfish they had eaten were reasonable evidence that the food poisoning was directly associated with histamine intoxication.

Rolle der basophilen Leukozyten bei entz�ndlichen Hauterkrankungen

Basophilic leukocytes are effector cells of the peripheral blood. They have several morphological and functional characteristics in common with tissue mast cells, such as expression of the high-affinity IgE receptor (Fc epsilon RI) and a high content of histamine within their granules. Functional comparison of human basophils and human mast cells isolated from different tissues revealed marked heterogeneity of mediator release after incubation with different secretagogues. Owing to their wide range of surface receptors, their (pro)inflammatory mediators released after activation, their mobility, and their rapid turnover, basophils appear basically to be potent effector cells, which migrate transiently into the skin during IgE-mediated (and/or IgE-independent) inflammatory reactions. The present paper reviews recent findings on the possible role of basophils for different immune reactions of the skin. Inhibition of basophil (and/or mast cell) activity seems to be necessary for both effective prophylaxis and therapy of allergic and inflammatory skin diseases. To date, however, the pharmacological modulation of mediator release from basophils lacks potent clinically useful compounds that can suppress the cellular response, since mast cell stabilizers such as cromoglycate and nedocromil are not effective. With a view to the development of active compounds, further in vitro studies should focus on the mechanisms of cell activation.