Histamine H1 Antagonists ; pharmacology ; Humans

OBJECTIVETo investigate the effects and the mechanisms of the first-generation histamine H(1)-antagonist diphenhydramine and the second-generation histamine H(1)- antagonist fexofenadine on seizure development of pentylenetetrazole (PTZ)-induced kindling in rats.

METHODSThe first-or second-generation histamine H(1)-antagonists and/or histidine were ip injected in rats every 48 h, followed by a subconvulsive dose of PTZ (35 mg/kg). Then the behavioral changes were observed for 30 min after every injection of PTZ. The histamine content of brain was measured spectrofluorometrically.

RESULTCompared with the control group, diphenhydramine (5 mg/kg) significantly augmented the severity of seizure development of PTZ-induced kindling, whereas fexofenadine (5 mg/kg) had no marked influence. The effects of diphenhydramine were antagonized by histidine, the precursor of histamine.

CONCLUSIONSeizure development of PTZ-induced kindling is promoted by the first-but not the second generation histamine H(1)-antagonists via the blockade of brain histamine H(1)-receptor.

Animals ; Histamine ; physiology ; Histamine H1 Antagonists ; pharmacology ; Histamine H1 Antagonists, Non-Sedating ; pharmacology ; Histidine ; pharmacology ; Kindling, Neurologic ; drug effects ; Male ; Pentylenetetrazole ; Rats ; Rats, Sprague-Dawley ; Seizures ; chemically induced

The present study was carried out to determine the role of histamine H(1) and H(2) receptors in the generation of basic respiratory rhythm. Neonatal (aged 0-3 d) Sprague-Dawley rats of either sex were used. The medulla oblongata slice containing the medial region of the nucleus retrofacialis (mNRF) and the hypoglossal nerve rootlets was prepared and the surgical procedure was performed in the modified Kreb's solution (MKS) with continuous carbogen (95% O(2) and 5% CO(2)), and ended in 3 min. Respiratory rhythmical discharge activity (RRDA) of the rootlets of hypoglossal nerve was recorded by suction electrode. Thirty medulla oblongata slice preparations were divided into 5 groups. In groups I, II and III, histamine (5 μmol/L), H(1) receptor specific antagonist pyrilamine (10 μmol/L) and H(2) receptor specific antagonist cimetidine (5 μmol/L) was added into the perfusion solution for 15 min separately. In group IV, after application of histamine for 15 min, additional pyrilamine was added into the perfusion for another 15 min. In group V, after application of histamine for 15 min, additional cimetidine was added into the perfusion for another 15 min. The discharges of the roots of hypoglossal nerve were recorded. Signals were amplified and band-pass filtered (100-3.3 kHz). Data were sampled (1-10 kHz) and stored in the computer via BL-420 biological signal processing system. Our results showed that histamine significantly decreased the respiratory cycle (RC) and expiratory time (TE), but changes of integral amplitude (IA) and inspiratory time (TI) were not statistically significant. Pyrilamine induced significant increases in RC and TE, but changes of TI and IA were not statistically significant. Cimetidine had no effects on RC, TE, TI and IA of RRDA. The effect of histamine on the respiratory rhythm was reversed by additional application of pyrilamine but not cimetidine. Taken together, with the results mentioned above, histamine H(1) receptors but not H(2) receptors may play an important role in the modulation of RRDA in the medulla oblongata slice preparation of neonatal rats.
Animals ; Animals, Newborn ; Cimetidine ; pharmacology ; Female ; Histamine ; pharmacology ; Histamine H1 Antagonists ; pharmacology ; Histamine H2 Antagonists ; pharmacology ; Hypoglossal Nerve ; physiology ; In Vitro Techniques ; Male ; Medulla Oblongata ; physiology ; Pyrilamine ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Histamine H1 ; physiology ; Receptors, Histamine H2 ; physiology ; Respiration

Degranulation of the mast cell has been reported by the injection of histamine liberators and other chemical agents. Chlorpheniramine maleate (1.2mg./kg. and 0.3mg./kg. comprising 1/74and 1/290 of LD50 respectively), which is an antihistamine agent, in physiological saline solution for intravenous injection and in Tyrode solution for intraperitoneal injection were given in single dose. The mesenteric mast cells stained in Pugh solution, as applied by Lee (1968), were counted according to the classification of An (1964) in 4 types; the typical normal mast cell, the Grade I type of mast cell, the Grade II type of mast cell and the Grade III type of mast cell. In the experimental rats given 1.2mg./kg. of chlorpheniramine intravenously, more mesenteric mast cells were s1ightly degranulated than those cells of the rats given 0.3mg./kg. of chlorpheniramine and the control rats. In the experimental rats given 1.2mg./kg. and 0.3 mg./kg. of chlorpheniramine intraperitoneally, more mesenteric mast cells were slightly degranulated than those cells of the control rats. However, in this intraperitoneal study the degree, or severity, of degranulation of the mesenteric mast cell was not in direct proportion to the dosage of this antihistamine. Consequently it is deduced that the experimental dosage of the antihistamine chlorpheniramine maleate, applied 1/74 and l/290 of LD50, caused an evient degranulation of mesenteric mast cells of the albino rats associated with probable histamine liberation.
Animal ; Chlorpheniramine/pharmacology ; Cytoplasmic Granules* ; Female ; Histamine H1 Antagonists/pharmacology* ; Male ; Mast Cells/drug effects* ; Rats

AIMTo determine the effect of histamine on ischemia-induced cellular edema and viability reduction in rat hippocampal slices, and the involved subtypes of histamine receptor in this effect.

METHODSIn vitro ischemic injury of hippocampal slices was induced by oxygen-glucose deprivation (OGD). The slice injury was determined by real-timely measuring the changes of light transmittance (LT) for the cellular edema in CA1 region of the hippocampal slice, and by detecting the product of 2, 3, 5-triphenyltetrazolium chloride (TTC), formazan, for the slice viability. The effect of histamine at various concentrations on the slice injury was observed, and the blockage by antagonists of histamine receptors was also investigated.

RESULTSHistamine (0.01-10 micromol x L(-1)) inhibited the peak value of LT during OGD in hippocampal slices and improved the reduced viability after OGD. Diphenhydramine (0.1-10 micromol x L(-1)), an H1 receptor antagonist, did not affect the effect of histamine, while cimetidine (0.1-10 micromol x L(-1)), an H2 receptor antagonist, partly abolished the protective effect of histamine.

CONCLUSIONHistamine protects hippocampal slices against ischemia-induced cellular edema and viability reduction; this effect might be mediated via, at least partly, H2 receptor.

Animals ; Cell Hypoxia ; Cell Survival ; drug effects ; Cimetidine ; pharmacology ; Diphenhydramine ; pharmacology ; Formazans ; metabolism ; Glucose ; deficiency ; Hippocampus ; drug effects ; metabolism ; pathology ; Histamine ; pharmacology ; Histamine H1 Antagonists ; pharmacology ; Histamine H2 Antagonists ; pharmacology ; Male ; Neuroprotective Agents ; pharmacology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate histamine-induced changes of the intracortical vessels in the cortical slice of rat brain.

METHODSImmunohistochemistry was employed to detect the expression of H1 and H2 receptors in the intracortical blood vessels of rats. Histamine-induced constriction of the intracortical blood vessels of the brain slices was observed with differential interference contrast microscope. Measurements of the luminal diameter were made on-line during the course of the experiment and confirmed off-line from the stored images. In order to observe whether histamine H1 and H2 receptors affected histamine-induced constriction, the intracortical blood vessels in the brain slices were pre-treated with H1 receptor antagonist diphenhydramine and H2 receptor antagonist cimetidine.

RESULTSExpression of H1 and H2 receptors was detected in the intracortical blood vessels of the rat brain. Histamine (1-100 micromol/L) induced a concentration-dependent constriction from (1.48-/+0.67)% to (32.91-/+7.91)%. The reactions to each histamine concentration were significantly (P<0.01) different from each other, with the exception of the highest histamine concentrations (30 and 100 micromol/L) when maximal constriction due to histamine were observed (P>0.05). With pre-treatment of the slice with 10 micromol/L diphenhydramine, application of histamine did not elicit constriction. Pre-treatment of the slice with 10 micromol/L cimetidine did not completely inhibit but somehow significantly weakened vascular constriction in response to histamine treatment at 10 and 30 micromol/L (P<0.05).

CONCLUSIONHistamine can induce constriction of the intracortical blood vessels, which is mediated by H1 receptor.

Animals ; Blood Vessels ; drug effects ; metabolism ; physiology ; Cerebral Cortex ; blood supply ; Cimetidine ; pharmacology ; Diphenhydramine ; pharmacology ; Histamine ; pharmacology ; Histamine H1 Antagonists ; pharmacology ; Histamine H2 Antagonists ; pharmacology ; In Vitro Techniques ; Male ; Rats ; Rats, Sprague-Dawley ; Receptors, Histamine H1 ; metabolism ; physiology ; Receptors, Histamine H2 ; metabolism ; physiology ; Vasoconstriction ; drug effects

OBJECTIVETo observe the inhibitory effect of mizolastine on substance P(SP)-induced production of leukotriene B(4) (LTB(4)) and interleukin 5 (IL-5) in mouse skin.

METHODSMice were fed with different doses of mizolastine or other control drugs, 30 min after administration animals were injected intradermally with SP on the back. The treated skin samples were taken and competitive enzyme-link immunoassay (ELISA) method was applied to detect LTB (4) and IL-5 in the skin samples.

RESULTThe LTB(4) and IL-5 levels in 10 mg/kg mizolastine group were (1.23 +/-0.29)pg/ml and (34.28 +/-11.00)pg/ml, respectively, which were lower than those in saline control group [(5.52+/-1.88)pg/ml and (179.62 +/-46.25)pg/ml respectively] or loratadine group [(3.89+/-1.27)pg/ml and (127.74 +/-43.27)pg/ml respectively]. No significant difference was found between 10 mg/kg mizolastine group and dexamethasone group (P=0.161 and P=0.508).

CONCLUSIONMizolastine might inhibit the production of LTB(4) and IL-5 induced by substance P in mouse skin, suggesting that anti-inflammatory effect and the blockade of histamine H1 receptors might be involved in its anti-pruritic mechanisms.

Animals ; Benzimidazoles ; pharmacology ; Female ; Histamine H1 Antagonists ; pharmacology ; Interleukin-5 ; biosynthesis ; Leukotriene B4 ; biosynthesis ; Male ; Mice ; Mice, Inbred BALB C ; Skin ; metabolism ; Substance P ; antagonists & inhibitors

OBJECTIVETo investigate the antagonistic effect and mechanism of the effect of cyproheptadine (Cyp) on endotoxic shock in rats.

METHODSEndotoxic shock was produced in rats by i.v. injection of lipopolysaccharides (LPS) (5 mg/kg). Tumor necrosis factor (TNF(alpha)) mRNA expression was assessed by Northern blot. Plasma TNF(alpha) content was measured by radioimmunoassay. Plasma superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were measured. The intracellular free calcium concentration ([Ca(2+)](i)) in single endothelial cells was determined by laser scanning confocal microscopy (LSCM).

RESULTSCyp 5 mg/kg injected immediately after i.v. LPS raised the mean arterial blood pressure (MABP) of shocked rats and improved their 24 h survival rate. Meanwhile, Cyp markedly decreased TNF(alpha) mRNA levels in rat liver (18 +/- 10 vs. LPS + saline 38 +/- 10, P < 0.01) as well as plasma TNF(alpha) content [(7.8 +/- 2.4) microg/L vs. LPS + saline (21.5 +/- 3.2) microg/L, P < 0.01)]. It enhanced plasma SOD activity [(1037.2 +/- 112.8) NU/L vs LPS + saline (615.4 +/- 92.6) NU/L, P < 0.01], reduced the MDA content [(5.2 +/- 1.1) micromol/L vs. LPS + saline (9.8 +/- 1.5) micromol/L, P < 0.01], and inhibited TNF(alpha)-induced [Ca(2+)](i) elevation.

CONCLUSIONCyp exerts an anti-endotoxic shock effect by inhibiting TNF(alpha) gene expression, enhancing SOD activity, reducing lipid peroxidation, and preventing [Ca(2+)](i) overload.

Animals ; Cyproheptadine ; pharmacology ; Histamine H1 Antagonists ; pharmacology ; Malondialdehyde ; blood ; Rats ; Rats, Wistar ; Shock, Septic ; drug therapy ; metabolism ; Superoxide Dismutase ; blood ; Tumor Necrosis Factor-alpha ; biosynthesis ; genetics

AIMTo study the intervention of cetirizine on monocyte chemoattractant protein-1 (MCP-1) in different cutaneous inflammation models.

METHODSHistamine and IFN-gamma stimulated dermal fibroblast cells and HaCaT cells to mimic cutaneous inflammation. Expression of MCP-1 was assessed by means of RT-PCR and ELISA.

RESULTSCompared with the control group of dermal fibroblast (DF) cells and HaCaT cells, MCP-1 mRNA was significantly upregulated by histamine (10 micromol x L(-1)) and IFN-gamma (20 ng x mL(-1)). The protein secretions of MCP-1 were increased 3.5 fold and 8.4 fold in DF cells, respectively. The similar tendency was observed in HaCaT cells. The enhancing effects of histamine and IFN-gamma on MCP-1 protein production were significantly inhibited by cetirizine (1 and 10 micromol x L(-1)) in DF and HaCaT cells.

CONCLUSIONCetirizine may exert the anti-inflammatory effect of skin via inhibiting MCP-1 expression.

Cell Line ; Cells, Cultured ; Cetirizine ; pharmacology ; Chemokine CCL2 ; biosynthesis ; genetics ; Dermatitis ; metabolism ; Dermis ; cytology ; Fibroblasts ; cytology ; metabolism ; Histamine ; pharmacology ; Histamine H1 Antagonists, Non-Sedating ; pharmacology ; Humans ; Interferon-gamma ; pharmacology ; Keratinocytes ; cytology ; metabolism ; RNA, Messenger ; biosynthesis ; genetics

To investigate the effects of neuronal histamine on spatial memory acquisition impairment in rats with pentylenetetrazole-kindling epilepsy, and to explore its mechanisms.A subconvulsive dose of pentylenetetrazole (35 mg/kg) was intraperitoneally injected in rats every 48 h to induce chemical kindling until fully kindled. Morris water maze was used to measure the spatial memory acquisition of the rats one week after fully pentylenetetrazole-kindled, and the histamine contents in different brain areas were measured spectrofluorometrically. Different dosages of hitidine (the precursor of histamine), pyrilamine (H1 receptor antagonist), and zolantidine (H2 receptor antagonist) were intraperitoneally injected, and their effects on spatial memory acquisition of the rats were observed.Compared with control group, escape latencies were significantly prolonged on Morris water maze training day 2 and day 3 in pentylenetetrazole-kindling epilepsy rats (all<0.05); and the histamine contents in hippocampus, thalamus and hypothalamus were decreased significantly (all<0.05). Escape latencies were markedly shortened on day 3 by intraperitoneally injected with histidine 500 mg/kg, and on day 2 and day 3 by intraperitoneally injected with histidine 1000 mg/kg in pentylenetetrazole-kindling epilepsy rats (all<0.05). The protection of histidine was reversed by zolantidine (10 and 20 mg/kg), but not by pyrilamine.Neuronal histamine can improve the spatial memory acquisition impairment in rats with pentylenetetrazole-kindling epilepsy, and the activation of H2 receptors is possibly involved in the protective effects of histamine.
Animals ; Benzothiazoles ; pharmacology ; Brain Chemistry ; drug effects ; Epilepsy ; chemically induced ; complications ; Hippocampus ; chemistry ; Histamine H1 Antagonists ; pharmacology ; Histamine H2 Antagonists ; pharmacology ; Histidine ; pharmacology ; Hypothalamus ; chemistry ; Kindling, Neurologic ; physiology ; Memory Disorders ; drug therapy ; etiology ; Pentylenetetrazole ; Phenoxypropanolamines ; pharmacology ; Piperidines ; pharmacology ; Pyrilamine ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Histamine H2 ; drug effects ; physiology ; Spatial Memory ; drug effects ; Spectrometry, Fluorescence ; Thalamus ; chemistry