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PubMed1990

Gastrointestinal histamine and histamine formation capacity after gastric irradiation in mice.

Mice were exposed to a single dose of 9 or 15 Gy of X rays directed to the stomach. Histamine and histamine formation capacity (HFC) in the oxyntic region of the stomach were assayed at regular intervals for 7 weeks. After 9 Gy, mean gastric mural histamine fell to 61% of the control value (p less than 0.01) 7 days after irradiation while HFC rose to 172% (p less than 0.05). Both histamine and HFC returned to control values within 2 weeks after irradiation. With 15 Gy, on Day 7, histamine fell to 46% (p less than 0.01) and HFC rose to 260% (p less than 0.05). Histamine concentration remained low (less than half of the control value) while HFC returned to normal. These dose-dependent changes in histamine were observed neither elsewhere in the gut nor in the circulating blood. Further groups of mice were exposed to 3, 6, 9 or 15 Gy to the stomach, with gastric histamine and HFC assayed on Day 7. Histamine concentration was inversely related to dose (r = -0.59, p less than 0.001) and HFC was directly dose dependent (r = 0.52, p less than 0.001). These results suggest that irradiation of the stomach may reduce gastric histamine without inducing a general histamine release. The depletion of the gastric histamine store may explain the inhibitory effect of irradiation of the stomach on gastric acid secretion.

Animals↗
PubMed1991

IL-8 inhibits histamine release from human basophils induced by histamine-releasing factors, connective tissue activating peptide III, and IL-3.

We have previously purified and partially characterized histamine releasing factors (HRF), which were derived from a mixture of human mononuclear cells and platelets. We now report the effect of IL-8 upon HRF-, connective tissue activating peptide III (CTAP III)-, and IL-3-induced histamine release from human basophils. We determined that IL-8 itself, at concentrations between 10(-7) to 10(-11) M, does not release histamine from basophils, although positive results are observed in two of 26 subjects at 10(-7) M. Unfractionated (crude) HRF released histamine in 25 of 26 donors, in the range of 6.7% to 100% of total basophil histamine stores. When basophils were preincubated with IL-8 (10(-7) to 10(-11) M) for 5 min, followed by a 40-min incubation with HRF, histamine release was significantly inhibited in 20 of 25 donors. Inhibition was observed at as little as 10(-11) M IL-8, with maximal inhibition being attained at 10(-9) M. HRF-containing supernatants contain a mixture of different histamine-releasing moieties. To better define which factor(s) may be inhibited by IL-8, fractionated supernatants, purified CTAP III, and IL-3 were studied. Histamine release produced by two different HRF-containing chromatographic fractions (HRFvoid and HRFpeak 2) and purified CTAP-III (5 micrograms/ml) was inhibited by IL-8 in 10 of 12 donors, three of three donors, and seven of 10 donors, respectively. IL-3 (5000 U/ml)-dependent histamine release was inhibited by IL-8 in all subjects tested. In contrast, histamine release by anti-IgE and FMLP was not affected by IL-8. Thus, IL-8 appears to be an inhibitor of cytokine-like molecules that induce histamine release and may represent the previously described 8-kDa histamine release inhibitory factor present in mononuclear cell supernatants.

Basophils↗
PubMed1996

The agonistic binding site at the histamine H2 receptor. II. Theoretical investigations of histamine binding to receptor models of the seven alpha-helical transmembrane domain.

In the first part (pp. 461-478 in this issue) of this study regarding the histamine H2 receptor agonistic binding site, the best possible interactions of histamine with an alpha-helical oligopeptide, mimicking a part of the fifth transmembrane alpha-helical domain (TM5) of the histamine H2 receptor, were considered. It was established that histamine can only bind via two H-bonds with a pure alpha-helical TM5, when the binding site consists of Tyr182/Asp186 and not of the Asp186/Thr190 couple. In this second part, two particular three-dimensional models of G-protein-coupled receptors previously reported in the literature are compared in relation to agonist binding at the histamine H2 receptor. The differences between these two receptor models are discussed in relation to the general benefits and limitations of such receptor models. Also the pros and cons of simplifying receptor models to a relatively easy-to-deal-with oligopeptide for mimicking agonistic binding to an agonistic binding site are addressed. Within complete receptor models, the simultaneous interaction of histamine with both TM3 and TM5 can be analysed. The earlier suggested three-point interaction of histamine with the histamine H2 receptor can be explored. Our results demonstrate that a three-point interaction cannot be established for the Asp98/ Asp186/Thr190 binding site in either of the investigated receptor models, whereas histamine can form three H-bonds in case the agonistic binding site is constituted by the Asp98/Tyr182/Asp186 triplet. Furthermore, this latter triplet is seen to be able to accommodate a series of substituted histamine analogues with known histamine H2 agonistic activity as well.

Binding Sites↗
PubMed1982

Effects of infused histamine: correlation of plasma histamine levels and symptoms.

Plasma and urine histamine levels were measured during sequential infusions of histamine (0.05, 0.1, 0.25, 0.5, and 1.0 microgram/kg/min histamine base for 30 min each) to determine the plasma level required to elicit flushing, headaches, tachycardia, and diastolic hypotension. Each study was performed with subjects on no medications or after pretreatment with hydroxyzine and/or cimetidine in order to confirm the receptor subtype involved in each of the responses. Resting plasma histamine levels were 0.62 +/- 0.12 ng/ml, and levels rose progressively indirect proportion to the concentration of infused histamine. Plasma levels of histamine required to elicit symptoms were as follows: 1.61 +/- 0.30 ng/ml = 30% increase in heart rate, 2.39 +/- 0.52 ng/ml = significant flush and headache, and 2.45 +/- 0.13 ng/ml = 30% increase in pulse pressure. Cimetidine pretreatment failed to influence the histamine level required to elicit symptoms, hydroxyzine pretreatment significantly raised the level required to increase heart rat by 30%, and the combination of antihistamines significantly raised the threshold for histamine to elicit all the response. Urine histamine was increased in direct proportion to the histamine infusions, and because of stability, accessibility, and the capacity for retrospective diagnosis, urine is the suggested fluid to employ to measure histamine release in humans.

Adult↗
PubMed1996

Selective effect of levocabastine on histamine receptor and histamine release from human leukocytes and guinea pig isolated tissue.

BACKGROUND: Levocabastine is a potent histamine H1 receptor antagonist used topically in the treatment of patients with allergic rhinitis. It has been suggested that antihistamines also have anti-inflammatory properties. OBJECTIVE: The present study was performed to investigate whether levocabastine, in addition to the anti-H1 receptor activity, has anti-inflammatory properties and thus is able to modulate the release of histamine and cytokines, such as interleukin 5 from human leukocytes and isolated tissues. METHODS: Leukocytes suspensions were prepared by dextran sedimentation of peripheral venous blood drawn from allergic and healthy volunteers. Leukocytes obtained from allergic volunteers were preincubated for 30 minutes with levocabastine (doses 10(-8) M to 10(-6) M) and thereafter incubated with allergen. Leukocytes obtained from healthy volunteers were incubated for zero to three hours with levocabastine (doses 10(-14) M to 10(-3) M). Histamine release was measured by an automated fluorometric method. Interleukin-5 release was measured by enzyme linked immunoassay. Contractile responses to histamine on guinea pig trachea and lung parenchyma as well as the release of histamine and interleukin-5 by the tissues were investigated in the absence or presence of levocabastine and/or the histamine H2 receptor antagonist cimetidine. RESULTS: Levocabastine did not influence allergen-induced histamine release from leukocytes obtained from allergic volunteers. High concentrations (10(-4)and 10(-3) M) of levocabastine, however, caused release of histamine from leukocytes obtained from healthy volunteers as well as guinea pig airway smooth muscle tissues. Pretreatment with levocabastine dose-dependently decreased the contractile response to histamine, showing an irreversible competitive mechanism. Interleukin 5 release from human leukocytes and by guinea pig airway smooth muscle was not detectable. CONCLUSIONS: These findings indicate that the H1 receptor blocker, levocabastine, has probably no anti-inflammatory properties, measured as histamine release, and that the histamine release from both human leukocytes and guinea pig trachea and lung parenchyma is significantly increased by the drug only at high concentrations.

Adult↗
PubMed1992

Molecular basis for the interaction of histamine with the histamine H2 receptor.

We undertook these studies to characterize the molecular basis of the interaction of histamine with the H2 receptor. Key areas of homology in the structures of the histamine H2 and beta 2 adrenergic receptor suggested specific transmembrane amino acids that might be important for binding of histamine. A third transmembrane aspartic acid of the histamine receptor (Asp98), thought to serve as a counter anion that interacts with the cationic amine moiety of histamine, was mutated to Asn98, and the mutated receptor was expressed in Hepa cells. Removal of the negatively charged amino acid abolished both binding of the H2 receptor antagonist [methyl-3H]tiotidine and histamine stimulated increases in cellular cAMP content. Mutation of a fifth transmembrane aspartic acid (Asp186) to Ala186 or Asn186 by itself or in conjunction with mutation of another fifth transmembrane amino acid (Thr190 to Ala190) resulted in a loss of [methyl-3H] tiotidine binding, although the generation of cAMP in response to histamine was maintained. The histamine receptor with only a Thr190 to Ala190 or Cys190 mutation retained the ability to bind [methyl-3H]tiotidine, but both the affinity and efficacy of binding were reduced. These data lead us to propose a model for histamine binding in which Asp98 is essential for histamine binding and action, Asp186 defines H2 selectivity, and Thr190 is important in establishing the kinetics of histamine binding, but is not essential for H2 selectivity.

Amino Acid Sequence↗
PubMed2006

Multiple role of histamine H1-receptor-PKC-MAPK signalling pathway in histamine-stimulated nerve growth factor synthesis and secretion.

Histamine is a potent stimulator of nerve growth factor (NGF) production in the central nerve system and in the periphery as well. In this review, the biochemical mechanisms of histamine-stimulated NGF synthesis and secretion, and interactions between histamine, interleukin-1beta, and interleukin-6 are discussed. The main signalling pathway, involved in the stimulation of NGF production by histamine, includes activation of histamine H(1)-receptor, stimulation of Ca(2+)-dependent protein kinase C and mitogen-activated protein kinase. The same signalling pathway is involved in the interactions between histamine, interleukin-1beta, and interleukin-6, where NGF secretion is amplified. Whereas histamine and interleukin-1beta cause additive stimulatory effect on NGF secretion, interaction between histamine and interleukin-6 causes a long-term synergism. Thus, activation of histamine H(1)-receptor-protein kinase C-mitogen-activated protein kinase signalling pathway plays a crucial role not only in the direct stimulation of NGF secretion by histamine, but also in the indirect stimulation via different types of interactions between histamine, interleukin-1beta, and interleukin-6, which may have important therapeutic implications in modulation of NGF production.

Animals↗
PubMed2003

Brain histamine and histamine H3 receptors following repeated L-histidine administration in rats.

In order to assess the importance of the chronic increase in precursor availability on central histaminergic mechanisms in rats, nine male Wistar rats received L-histidine orally at a dose of 1000 mg/kg, twice daily (07.00 h and 19.00 h) for 1 week; 9 rats were used as controls. Brain tissue histamine and tele-methylhistamine levels, as well as plasma histamine concentration were assayed. Binding properties and regional distribution of the autoregulatory histamine H3 receptors in brain were studied with [3H]-R-alpha-methylhistamine receptor binding and autoradiography. In L-histidine loaded rats, tissue histamine levels in cortex, hypothalamus, and rest of the brain were significantly increased by 40%-70%. Histamine concentrations in cerebellum and plasma, and tele-methylhistamine concentrations in cortex and hypothalamus did not change. The binding properties of H3 receptors in cortex were not altered. However, there were changes in the regional distribution of [3H]-R-alpha-methylhistamine binding sites, suggestive of a region-selective up-/down-regulation of histamine H3 receptors or their receptor sub-types. These results imply that following repeated L-histidine administration in the rat (1) there is enhanced synthesis of brain histamine not reflected in its functional release; (2) the excess of histamine is sequestered and stored rather than being metabolized; (3) histamine H(3) receptor binding properties are not altered, whereas receptor density is changed in selected regions. In conclusion, these results demonstrate that the neuronal mechanisms controlling histamine synthesis, storage, and release are adaptable and allow the sequestration of the excess of histamine in order to prevent excessively high neuronal activity.

Administration, Oral↗
PubMed2002

Membrane-bound histamine N-methyltransferase in mouse brain: possible role in the synaptic inactivation of neuronal histamine.

In the CNS, histamine is a neurotransmitter that is inactivated by histamine N-methyltransferase (HNMT), a soluble enzyme localized to the cytosol of neurons and endothelial cells. However, it has not been established how extracellular histamine, a charged molecule at physiological pH, reaches intracellular HNMT. Present studies investigated two potential routes of histamine inactivation in mouse brain nerve terminal fractions (synaptosomes): (i) histamine uptake and (ii) histamine metabolism by HNMT. Intact synaptosomes demonstrated a weak temperature-dependent histamine uptake (0.098 pmol/min-mg protein), but contained a much greater capacity to metabolize histamine by HNMT (1.4 pmol/min-mg protein). Determination of the distribution of HNMT within synaptosomes revealed that synaptosomal membranes (devoid of soluble HNMT) contribute HNMT activity equivalent to intact synaptosomes (14.3 +/- 2.2 and 18.2 +/- 4.3 pmol/min-tube, respectively) and suggested that histamine-methylating activity is associated with the membrane fraction. Additional experimental findings that support this hypothesis include: (i) the histamine metabolite tele-methylhistamine (tMH) was found exclusively in the supernatant fraction following an HNMT assay with intact synaptosomes; (ii) the membrane-bound HNMT activity was shown to increase 6.5-fold upon the solubilization of the membranes with 0.1% Triton X-100; and (iii) HNMT activity from the S2 fraction, ruptured synaptosomes, and synaptosomal membranes displayed different stability profiles when stored over 23 days at - 20 degrees C. Taken together, these studies demonstrate functional evidence for the existence of membrane-bound HNMT. Although molecular studies have not yet identified the nature of this activity, the present work suggests that levels of biologically active histamine may be controlled by an extracellular process.

Animals↗
PubMed2006

Ascorbate enhancement of H1 histamine receptor sensitivity coincides with ascorbate oxidation inhibition by histamine receptors.

Ascorbate has previously been shown to enhance both alpha(1)- and beta(2)-adrenergic activity. This activity is mediated by ascorbate binding to the extracellular domain of the adrenergic receptor, which also decreases the oxidation rate of ascorbate. H1 histamine receptors have extracellular agonist or ascorbate binding sites with strong similarities to alpha(1-) and beta(2)-adrenergic receptors. Physiological concentrations of ascorbate (50 microM) significantly enhanced histamine contractions of rabbit aorta on the lower half of the histamine dose-response curve, increasing contractions of 0.1, 0.2, and 0.3 microM histamine by two- to threefold. Increases in ascorbate concentration significantly enhanced 0.2 microM histamine (5-500 microM ascorbate) and 0.3 microM histamine (15-500 microM ascorbate) in a dose-dependent manner. Histamine does not measurably oxidize over 20 h in oxygenated PSS at 37 degrees C. Thus the ascorbate enhancement is independent of ascorbate's antioxidant effects. Ascorbate in solution oxidizes rapidly. Transfected histamine receptor membrane suspension with protein concentration at >3.1 microg/ml (56 nM maximum histamine receptor) decreases the oxidation rate of 392 microM ascorbate, and virtually no ascorbate oxidation occurs at >0.0004 mol histamine receptor/mol ascorbate. Histamine receptor membrane had an initial ascorbate oxidation inhibition rate of 0.094 min.microg protein(-1).ml(-1), compared with rates for transfected ANG II membrane (0.055 min.microg protein(-1).ml(-1)), untransfected membrane (0.052 min.microg protein(-1).ml(-1)), creatine kinase (0.0082 min.microg protein(-1).ml(-1)), keyhole limpet hemocyanin (0.00092 min.microg protein(-1).ml(-1)), and osmotically lysed aortic rings (0.00057 min.microg wet weight(-1).ml(-1)). Ascorbate enhancement of seven-transmembrane-spanning membrane receptor activity occurs in both adrenergic and histaminergic receptors. These receptors may play a significant role in maintaining extracellular ascorbate in a reduced state.

Amino Acid Sequence↗
PubMed1976

Effect of the histamine (H2) inhibitor metiamide on histamine-stimulated bile flow in dogs.

The effects of the histamine H2-receptor inhibitor metiamide on histamine-stimulated canine bile flow and gastric hydrogen ion output were evaluated. Histamine was found to stimulate bile volume in doses comparable to those that stimulated gastric hydrogen ion output; both responses appeared to have the same maximal response dose, 150 mug/kg per h. Metiamide alone did not alter hepatic bile flow. Administration of metiamide, 2 mg/kg per h, along with various doses of histamine demonstrated that the H2-receptor antagonist decreased bile volume and gastric hydrogen ion output from values obtained with histamine administration alone. The D50 of histamine for bile flow was 16.3 mug/kg per h and the D50 for hydrogen ion output was 44.2 mug/kg per h, Kinetic analysis suggests that the decrease in histamine-stimulated hydrogen ion output produced by metiamide is the result of competitive inhibition; the decrease in histamine-stimulated bile volume by metiamide which is different from the hydrogen ion inhibition, suggests noncompetitive inhibition. These data indicate that the mechanism of histamine choleresis is different from the mechanism of histamine-stimulated gastric acid output and that histamine-stimulated bile flow may not be the result of direct hormone-receptor interaction.

Animals↗
PubMedDate not supplied

[The effect of histamine and histamine H1 and H2 receptor blockers on the tone of the longitudinal muscles in the human appendix].

The aims of this study were to determine whether the effect of histamine on a smooth musculature of the human appendix is mediated by histamine H1-receptors only or whether histamine H2-receptors are involved, as well. The obtained results indicate histamine increases tonus in musculature; however, histamine H1-receptor antagonist (promethazine) decreases tonus. Histamine H2-receptor antagonist (cimetidine) has caused a mild increase in tonus of musculature what indicates that it has a certain intrinsic activity. By blocking histamine receptors with H1 and H2 antagonists which were used either separately or together before cumulative histamine concentrations, it has been concluded that histamine actions are exerted not exclusively by H1-receptors but also histamine H2-receptor antagonists can significantly decrease the tonicizing effect of histamine.

Appendix↗
PubMed1980

Evaluation of the role of Histamine H1- and H2-receptors in cutaneous inflammation in the guinea-pig produced by histamine and mast cell degranulation.

1 The role of histamine H1- and H2-receptors in mediating the cutaneous inflammatory response produced by exogenous histamine and the release of endogenous histamine from mast cells has been investigated by a method which permits simultaneous, quantitative measurement of vasodilatation, vascular permeability and oedema formation. 2 Histamine and the selective H1-receptor agonist, 2-(2-aminoethyl) pyridine, both produced vasodilatation, increased vascular permeability and oedema formation whereas the selective H2-receptor agonist, dimaprit, produced only vasodilatation. 3 Mepyramine and cimetidine both reduced the vasodilatation response to histamine, the combination of antagonists being superior to either antagonist alone. Mepyramine (but not cimetidine) virtually abolished extravascular albumin accumulation and oedema formation. 4 Mepyramine and cimetidine both reduced the vasodilatation response produced by active cutaneous anaphylaxis and compound 48/80. However, mepyramine was less effective in reducing the vascular permeability response to mast cell degranulation than to histamine. 5 In conclusion, the vasodilator response to histamine is mediated by both H1- and H2-receptors; the permeability response to histamine is mediated solely by H1-receptors. A combination of H1- and H2-receptor antagonists appears to be more effective than either antagonist alone in reducing cutaneous inflammatory reactions involving histamine.

Animals↗
PubMed1989

Role of calcium in histamine release from rat mast cells activated by various secretagogues; intracellular calcium mobilization correlates with histamine release.

Anti-IgE, con A or antigen caused an increase in the intracellular calcium concentration, [Ca2+]i, of mast cells. The increase occurred in two stages: a rapid initial rise caused by Ca-mobilization from intracellular Ca-stores and a second sustained rise caused by an influx of extracellular calcium (White, J.R., Pluznik, D.V., Ishizaka, K. & Ishizaka, T. (1985) Proc. Natl. Acad. Sci. U.S.A. 82, 8193-8197). The rapid initial rise was followed by a release of histamine, which seemed to coincide with the second rise. A23187 and compound 48/80 induced a rapid initial rise in [Ca2+]i, followed by a gradual decrease in [Ca2+]i, GMCHA-OPhBut, a specific pH 7 tryptase inhibitor (Muramatu, M., Ito, T., Takei, M. & Endo, K. (1988) Biol. Chem. Hoppe-Seyler 369, 617-625), strongly inhibited both the initial and second rises of [Ca2+]i, as well as histamine release by these secretagogues, and its effects on the initial rise were closely correlated with those on histamine release. Addition of GMCHA-OPhBut immediately after the initial rise strongly inhibited the second rise, thereby decreasing the final [Ca2+]i. These results strongly suggested a possible involvement of pH 7 tryptase, not only in Ca-mobilization leading to the initial rise in [Ca2+]i, but also in the second rise. Trapping of extracellular calcium by 3mM EGTA decreased both the initial rise in [Ca2+]i and histamine secretion induced by anti-IgE or con A; the magnitude of this effect depended on the time between induction and EGTA addition. Histamine release was closely correlated with the initial rise in [Ca2+]i. Similar results were obtained with A23187, but even 5 min after the addition of EGTA an initial rise of [Ca2+]i could still be induced, and histamine (30% of total histamine) was still released. However, A23187 did not induce a rise in [Ca2+]i in mast cells which had been exhaustively washed with Tyrode/Hepes solution containing 3mM EGTA, followed by suspension in the same solution. Even at 20 min after depletion of the extracellular calcium, compound 48/80 still caused an initial rise in [Ca2+]i to above half the maximal value, and histamine secretion was even less affected. The above results indicated that the initial rise in [Ca2+]i, due to Ca-mobilization, correlates with the histamine release promoted by the secretagogues described. On the other hand, isoproterenol strongly induced histamine secretion with no change of [Ca2+]i, while EGTA treatment prior to isoproterenol stimulation had no effect on histamine release, indicating a different secretion mechanism.

Aminoquinolines↗
PubMed2002

[Histamine receptors in the female reproductive system. Part I. Role of the mast cells and histamine in female reproductive system].

Histamine isolated from many different tissues, acts via three types of histamine receptors: H1, H2 and H3. In peripheral tissues histamine is mainly stored in mast cells (MC). Presence of mast cells was proved also in mammals' uteri. In human uterus the majority of mast cells are located close to smooth muscle cells. It might indicate that MC plays a role in tissue remodelling during the menstrual cycle. The quantity and activity of mast cells is in connection with hormonal status of the organism. Although there are some differences, human uterine mast cells are similar to the mast cells isolated from other tissues. It is suggested that histamine is important for normal ovulation, blastocyst implantation, placental blood flow regulation, lactation and contractile activity of uterus. Histamine may also play a role in pathological processes such as pre-eclampsia or preterm delivery. The participation of mast cells and histamine in blastocyst implantation is very controversial. In W/Wv mice (without mast cells) normal implantation was observed. It denies the main role of mast cells in this process but dos not exclude histamine action. In mice the major source of histamine are uterine epithelial cells during early pregnancy. The influence of cytokines on blastocyst implantation and the role of histamine in cytokines release from the uterine mast cells are also very unclear.

Animals↗
PubMed2004

Involvement of histamine H4 and H1 receptors in scratching induced by histamine receptor agonists in Balb C mice.

The role of histamine H(1), H(2), H(3) and H(4) receptors in acute itch induced by histamine was investigated in female BalbC mice. Scratching was induced by intradermal injections of pruritogen into the back of the neck and "itch" assessed by quantifying the scratching evoked. Histamine (0.03-80 micromol), histamine-trifluoromethyl-toluidine (HTMT, H(1) agonist, 0.002-2 micromol), clobenpropit (H(4) agonist, H(3) antagonist, 0.002-0.6 micromol) and to a lesser extent imetit (H(3)/H(4) agonist, 0.03-3 micromol) all induced dose-dependent scratching. Dimaprit (H(2) agonist, 0.04-40 micromol) did not cause scratching. Mepyramine (H(1) antagonist, 20 mg kg(-1), i.p.) reduced scratching evoked by histamine and HTMT, but not that caused by H(3) or H(4) agonists. Thioperamide (H(3)/H(4) antagonist, 20 mg kg(-1), i.p.) reduced scratching induced by histamine, H(3) and H(4) agonists, but not that caused by HTMT. The non-sedating H(1) antagonist, terfenadine, also significantly reduced the scratching induced by the H(1) agonist, HTMT. Cimetidine (H(2) antagonist, 20 mg kg(-1), i.p.) did not affect histamine-induced scratching. These results indicate that activation of histamine H(4) receptors causes itch in mice, in addition to the previously recognised role for H(1) receptors in evoking itch. Histamine H(4) receptor antagonists therefore merit investigation as antipruritic agents.

Animals↗
PubMed1995

Histamine-stimulated production of matrix metalloproteinase 1 by human rheumatoid synovial fibroblasts is mediated by histamine H1-receptors.

The purpose of this study was to investigate the role of histamine in human rheumatoid synovial fibroblasts in the production of factors responsible for tissue remodelling and cartilage breakdown in rheumatoid arthritis. We examined the effects of histamine of tritiated thymidine incorporation, production of matrix metalloproteinase-1 (MMP-1), histamine H1-receptor expression, phosphoinositide metabolism and intracellular calcium ion concentration ([Ca2+]i) in human rheumatoid synovial fibroblasts. Tritiated thymidine incorporation studies demonstrated that histamine markedly stimulated the proliferation of rheumatoid synovial fibroblasts. Immunofluorescence and Northern blot analyses revealed that proMMP-1 production was also stimulated by histamine. The levels of inositol phosphates and [Ca2+]i in the cells were elevated in response to histamine, indicating that the cells expressed histamine H1-receptors; and Northern blot analysis indicated that these H1-receptors were up-regulated by histamine. In in situ hybridization, large amounts of histamine H1-receptor mRNA were also detected in rheumatoid synovial tissue. These results suggest that the interaction between H1-receptor expression in rheumatoid synovial fibroblasts and histamine secretion by mast cells and macrophages in the affected sites is an important event responsible for tissue remodelling and joint destruction in rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed1983

Cutaneous histamine levels and histamine releasability from the skin in atopic dermatitis and hyper-IgE-syndrome.

We determined the histamine content in the skin of 22 adults with atopic dermatitis, one patient with hyper-IgE-syndrome, and 20 controls by the enzymatic double isotope assay. In addition, we performed a pilot study of histamine degradation in the skin. We tested, furthermore, the releasability of histamine from skin sections of patients with atopic dermatitis and healthy controls upon challenge with acetylcholine, anti-IgE, and compound 48/80. Histamine was also determined in 13 plasma specimens and was always less than 1 ng/ml. The mean +/- SEM histamine concentration in the skin was 196 +/- 30 ng/mg protein in controls and 262 +/- 68 ng/mg protein in atopic dermatitis (no statistically significant difference). One control and three patients with atopic dermatitis exhibited a slight, the hyper-IgE patient a marked, elevation of the skin histamine content. No gross differences in the degradation rate of histamine were observed between patients and controls. Acetylcholine and 48/80 induced the same histamine release in both groups; with anti-IgE, almost the double amount of histamine was released from the skin of atopic dermatitis patients as compared to controls. These findings suggest an enhanced releasability of histamine upon immunologic challenge in atopic dermatitis.

Adolescent↗