Lack of histamine synthesis and down-regulation of H1 and H2 receptor mRNA levels by dexamethasone in cerebral endothelial cells.
(1/301)
The purpose of this work was to determine whether cerebral endothelial cells have the capacity to synthesize histamine or to express mRNA of receptors that specifically respond to available free histamine. The histamine concentrations and the expression of L-histidine decarboxylase (HDC) and histamine H1 and H2 receptor mRNA, both in adult rat brain and in cultured immortalized RBE4 cerebral endothelial cells, were investigated. In this study endothelial cells were devoid of any kind of detectable histamine production, both in vivo and in the immortalized RBE4 cells in culture. Both the immunostainings for histamine and the in situ hybridizations for HDC were negative, as well as histamine determinations by HPLC, indicating that endothelial cells do not possess the capacity to produce histamine. Also, glucocorticoid (dexamethasone) treatment failed to induce histamine production in the cultured cells. Although the cerebral endothelial cells lack histamine production, a nonsaturable uptake in RBE4 cells is demonstrated. The internalized histamine is detected both in the cytoplasm and in the nucleus, which could indicate a role for histamine as an intracellular messenger. Histamine H1 and H2 receptor mRNA was expressed in RBE4 cells, and glucocorticoid treatment down-regulated the mRNA levels of both H1 and H2 receptors. This mechanism may be involved in glucocorticoid-mediated effects on cerebrovascular permeability and brain edema. (+info)
Tick histamine-binding proteins: isolation, cloning, and three-dimensional structure.
(2/301)
High-affinity histamine-binding proteins (HBPs) were discovered in the saliva of Rhipicephalus appendiculatus ticks. Their ability to outcompete histamine receptors indicates that they suppress inflammation during blood feeding. The crystal structure of a histamine-bound HBP, determined at 1.25 A resolution, reveals a lipocalin fold novel in containing two binding sites for the same ligand. The sites are orthogonally arranged and highly rigid and form an internal surface of unusual polar character that complements the physicochemical properties of histamine. As soluble receptors of histamine, HBPs offer a new strategy for controlling histamine-based diseases. (+info)
Human histamine H2 receptor gene: multiple transcription initiation and tissue-specific expression.
(3/301)
We have characterized the genomic structure of 12.3 kb of the 5'-flanking region of the human histamine H2 receptor gene. The multiple transcription initiation sites of the human histamine H2 receptor gene were mapped utilizing the 5'-end cap structure of mRNA. We found that a 85 bp segment (-610-(-)525 bp) immediately upstream of the initiation site exhibits a strong promoter activity in the gastric adenocarcinoma, MNK45, expressing human histamine H2 receptor. A 4.8 kb transcript of the human histamine H2 receptor gene was found in the placenta, spinal cord, lymph node and bone marrow in addition to the previously reported tissues including the heart, brain and stomach, whereas a 1.8 kb transcript was observed in almost all tissues examined. 3'-rapid amplification of cDNA ends revealed the corresponding length of the 3'-untranslated region. These results suggest that the 3'-untranslated region may be involved in the differential expression. (+info)
Effects of different subtypes of histamine receptors on proliferation and differentiation of murine colony forming unit granulocyte-macrophage and colony forming unit megakaryocyte.
(4/301)
OBJECTIVE: To investigate the function and characteristics of histamine receptors on the hemopoietic progenitor cells. METHODS: BDF1 mice (both male and female), inbred at our university, aged 8-12 weeks, weighing 20-24 g, were used in this study. Bone marrow cells were incubated for 1 hour at 37 degrees C with 2-AT (H1 receptor agonist) or impromidine (H2 receptor agonist) alone, or in combination with the antagonists pyrilamine or cimetidine respectively. Control experiment was performed in Dulbecco's modified Eagle's Medium (DMEM) alone. Cells treated with different drugs were performed by colony forming unit-granulocyte-macrophage (CFU-GM) and colony forming unit-megakaryocyte (CFU-Meg) assay. RESULTS: When bone marrow cells were treated with 10(-8) mol/L to 10(-5) mol/L of 2-thiazolylethylamine (2-AT) which had no influence on CFU-GM and CFU-Meg proliferation, 10(-8) mol/L to 10(-5) mol/L of impromidine could increase the number of CFU-GM and CFU-Meg colonies. The effects of H2 receptor agonists on CFU-GM, CFU-Meg could be antagonized by H1 receptor agonist. CONCLUSIONS: Our findings suggest the existence of histamine H1 and H2 receptors on the hemopoietic progenitor cells and the antagonism between two different histamine receptor subtypes on the proliferation of CFU-GM and CFU-Meg. (+info)
Cytological transformations associated with parietal cell stimulation: critical steps in the activation cascade.
(5/301)
Cultured rabbit parietal cells were used to evaluate morphological responses to activators and inhibitors of HCl secretion. Immunofluorescence was used to localize the proton pump protein, H, K-ATPase, and the apical membrane-cytoskeletal linker protein, ezrin; fluorescent-labeled phalloidin was used as a marker of F-actin. Treatment of healthy control parietal cells with secretagogues resulted in exaggerated swelling of apical membrane vacuoles, presumably with the accumulation of HCl and water. Thus stimulation-associated swelling of apical vacuoles was blocked by inhibitors that work at various steps in the secretion-activation cascade. When secretion was blocked by agents that prevent the translocation of H,K-ATPase-rich tubulovesicles to apical membrane vacuoles (such as H2-receptor antagonists and protein kinase A inhibitors), the general resting morphology was maintained. ME-3407 (a functional analogue of wortmannin) was unique in preventing H, K-ATPase redistribution and effecting the delocalization of ezrin from apical membrane vacuoles. When secretion was blocked by agents that inhibit the H+ pump or induce H+ backflux, the translocation of H,K-ATPase to apical membrane vacuoles occurred but the large vacuolar swelling associated with HCl and H2O accumulation was greatly diminished. These data support the membrane recycling/recruitment hypothesis of HCl secretion in which H, K-ATPase-rich tubulovesicles are recruited from a cytoplasmic domain to the apical surface, and they are inconsistent with models proposing that the tubulovesicles, regardless of shape, are contiguous with the apical plasma membrane. These studies also demonstrate the utility of the parietal cell culture model in distinguishing a general site of action for various inhibitors and antisecretory agents. (+info)
Histamine response and local cooling in the human skin: involvement of H1- and H2-receptors.
(6/301)
AIMS: Histamine may contribute locally to cutaneous blood flow control under normal and pathologic conditions. The objective of this study was to observe the influence of skin temperature on histamine vasodilation, and the roles of H1-and H2-receptors using novel noninvasive methods. METHODS: Eleven healthy subjects received, double-blind, single doses of the H1-receptor antagonist cetirizine (10 mg), cetirizine (10 mg) plus the H2-receptor antagonist cimetidine (400 mg), or placebo on separate occasions. Histamine was dosed cumulatively by iontophoresis to the forearm skin at 34 degrees C and 14 degrees C. Laser-Doppler flux (LDF) was measured at the same sites using customised probeholder/iontophoretic chambers with Peltier cooling elements. Finger mean arterial pressure (MAP) was measured and cutaneous vascular conductance calculated as LDF/MAP. RESULTS: Histamine vasodilation was reduced in cold skin. Cetirizine shifted the histamine dose-response at both temperatures: statistically significantly at 14 degrees C only. Combined H1- and H2-receptor antagonism shifted the response significantly at both temperatures. CONCLUSIONS: H1- and H2-receptors mediate histamine-induced skin vasodilation. The sensitivity of these receptors, particularly the H1- receptor, is attenuated at low skin temperature. Whether the reduced effect in cold skin represents specific receptor or postreceptor desensitization, or nonspecific attenuation of cutaneous vasodilation remains to be elucidated. (+info)
Role of neuropeptide-sensitive L-type Ca(2+) channels in histamine release in gastric enterochromaffin-like cells.
(7/301)
Peptides release histamine from enterochromaffin-like (ECL) cells because of elevation of intracellular Ca(2+) concentration ([Ca(2+)](i)) by either receptor-operated or voltage-dependent Ca(2+) channels (VDCC). To determine whether VDCCs contribute to histamine release stimulated by gastrin or pituitary adenylate cyclase-activating polypeptide (PACAP), the presence of VDCCs and their possible modulation by peptides was investigated in a 48-h cultured rat gastric cell population containing 85% ECL cells. Video imaging of fura 2-loaded cells was used to measure [Ca(2+)](i), and histamine was assayed by RIA. Cells were depolarized by increasing extracellular K(+) concentrations or by 20 mM tetraethylammonium (TEA(+)). Cell depolarization increased transient and steady-state [Ca(2+)](i) and resulted in histamine release, dependent on extracellular Ca(2+). These K(+)- or TEA(+)-dependent effects on histamine release from ECL cells were coupled to activation of parietal cells in intact rabbit gastric glands, and L-type channel blockade by 2 microM nifedipine inhibited 50% of [Ca(2+)](i) elevation and histamine release. N-type channel blockade by 1 microM omega-conotoxin GVIA inhibited 25% of [Ca(2+)](i) elevation and 14% of histamine release. Inhibition was additive. The effects of 20 mM TEA(+) were fully inhibited by 2 microM nifedipine. Both classes of Ca(2+) channels were found in ECL cells, but not in parietal cells, by RT-PCR. Nifedipine reduced PACAP-induced (but not gastrin-stimulated) Ca(2+) entry and histamine release by 40%. Somatostatin, peptide YY (PYY), and galanin dose dependently inhibited L-type Ca(2+) channels via a pertussis toxin-sensitive pathway. L-type VDCCs play a role in PACAP but not gastrin stimulation of histamine release from ECL cells, and the channel opening is inhibited by somatostatin, PYY, and galanin by interaction with a G(i) or G(o) protein. (+info)
Histamine induces melanogenesis and morphologic changes by protein kinase A activation via H2 receptors in human normal melanocytes.
(8/301)
Hyperpigmentation frequently accompanies chronic or acute inflammation. A number of inflammatory mediators have been shown to stimulate melanin synthesis in human melanocytes. Although histamine is ubiquitous as an inflammatory factor, its involvement in pigmentation remains obscure. In this work, we examined the effects of histamine on cultured human melanocytes. Treatment of human melanocytes with 0.1-10 microM histamine evoked morphologic changes and increases in tyrosinase activity. The concomitant increases in melanin content of the histamine-treated melanocytes indicated an elevation of melanin synthesis by tyrosinase activation. These stimulatory effects of histamine were completely inhibited by an H2 antagonist, famotidine, whereas H1 and H3 antagonists had no inhibitory effect whatsoever. In addition, an H2 agonist, dimaprit, induced the same degree of melanogenesis as histamine at concentrations of 0.1-10 microM. We observed an increase in the intracellular cAMP contents of human melanocytes induced by histamine via the H2 receptors. We know that this cAMP accumulation and subsequent protein kinase A activation plays a critical role in histamine-induced melanogenesis, because a specific protein kinase A inhibitor, H-89, completely suppressed these stimulatory effects of histamine, and because dibutylic cAMP, a specific protein kinase A activator, stimulated human melanocytes as potently as histamine. Taken together, we show here that histamine induces melanogenesis of human cultured melanocytes by protein kinase A activation via H2 receptors. (+info)