Effects of pH on vascular tone and L-type Ca2+ channels were investigated using Mulvany myograph and voltage-clamp technique in rabbit basilar arteries. In rabbitbasilar arteries, high K+ produced tonic contractions by 11+/-0.6 mN (mean+/-S.E., n=19). When extracellular pH (pHo) was changed from control 7.4 to 7.9 ([alkalosis]o), K+-induced contraction was increased to 128+/-2.1% of the control (n=13). However, K+-induced contraction was decreased to 73+/-1.3% of the control at pHo 6.8 ([acidosis]o, n=4). Histamine (10 micrometer) also produced tonic contraction by 11+/-0.6 mN (n=17), which was blocked by post-application of nicardipine (1 micrometer). [alkalosis]o and [acidosis]o increased or decreased histamine-induced contraction to 134+/-5.7% and 27+/-7.6% of the control (n=4, 6). Since high K+- and histamine-induced tonic contractions were affected by nicardipine and pHo, the effect of pHo on voltage-dependent L-type Ca2+ channel (VDCCL) was studied. VDCCL was modulated by pHo: the peak value of Ca2+ channel current (IBa) at a holding of 0 mV decreased in [acidosis]o by 41+/-8.8%, whereas that increased in [alkalosis]o by 35+/-2.1% (n=3). These results suggested that the external pH regulates vascular tone partly via the modulation of VDCC in rabbit basilar arteries.
Animals ; Arteries/*pathology ; Basilar Artery/*pathology ; Calcium/metabolism ; Calcium Channels/chemistry ; Electrophysiology ; Histamine/chemistry/metabolism ; Hydrogen-Ion Concentration ; Muscle Cells/cytology ; Muscle Contraction ; Muscle, Smooth/*pathology ; Patch-Clamp Techniques ; Potassium/chemistry/metabolism ; Rabbits ; Stress, Mechanical ; Time Factors

OBJECTIVE: To investigate the changes of leukotriene D4 (LTD4) in nasal discharge and plasma of patients with persistent allergic rhinitis (AR) and the effects of antihistamine. METHOD: The investigation was a prospective, randomized controlled trial. Forty AR patients (group C) were divided randomly into two subgroup. One group received oral antihistamine 10 mg everyday for one week (group CA) and another group received no loratadine tablets 10 mg everyday for one week (group CB). Fifteen age matched healthy (group D) people were enrolled as control. The level of LTD4 and interleukin-5 (IL-5) in both nasal discharge and plasma by using enzyme linked immunosorbent assay (ELISA) and enzyme immunoassay (EIA), cell counts and cell differentials in nasal discharge, were measured before and after three month. The clinical symptom and life quality scores of group C were also investigated. RESULT: The concentrations of LTD4 in nasal discharge [(794 +/- 305) pg] and plasma [(5219 +/- those in group D [(347 +/- 169) pg, (2283 +/- 489) ng/L, all P 1185) ng/L] in group C were significantly higher than those in group D [(347 +/- 169) pg, (2283 +/- 489) ng/L, all P < 0.05]. The level of LTD4 in nasal discharge was positively correlated with the percentage of neutrophil (r = 0.453, P < 0.05) and IL-5 (r = 0.364, P < 0.05). The pre- and post-therapy concentrations of nasal discharge and plasma in group CA were (812 +/- 1592) pg, (657 +/- 495) pg and (5422 +/- 935) ng/L, (4589 +/- 1057) ng/L respectively; While in group CB the concentrations were (776 +/- 227) pg, (860 +/- 194) pg and (5074 +/- 1850) ng/L, (6063 +/- 450) ng/L, respectively. There were no significant difference either in the level of LTD4 in nasal discharge or in plasma in both groups (all P > 0.05). CONCLUSION The results suggested that LTD4 was involved in airway inflammation in AR. Antihistamine was not effective enough in decreasing the levels of LTD4 in both nasal discharge and plasma of AR patients.
Adult ; Anti-Allergic Agents ; pharmacology ; Bodily Secretions ; chemistry ; Female ; Histamine H1 Antagonists ; pharmacology ; Humans ; Leukotriene Antagonists ; therapeutic use ; Leukotriene D4 ; analysis ; blood ; metabolism ; Male ; Middle Aged ; Plasma ; chemistry ; Prospective Studies ; Rhinitis, Allergic, Perennial ; blood ; drug therapy ; metabolism

OBJECTIVETo investigate the effect of Qingkailing injection (QKLI) on complement and RBL-2 H3 cells in virto.

METHODThe mixture of human serums and QKLI were incubated for 30 min in vitro and then the content of SC5 b-9 in the mixture was determined by ELISA. RBL-2 H3 cells were cultured and treated by QKLI. Beta-heosaminidase release rate was measured by coloration method. The content of histamine in supernatant was tested by ELISA.

RESULTThe QKLI can reduce the content of SC5 b-9 (P<0.05) and promote the release of beta-heosaminidase and histamine significantly (P<0.05).

CONCLUSIONQKLI didn't induce the complement activation, but induced the release of beta-heosaminidase and histamine directly. Therefore, the clinical adverse reactions of QKLI in clinic may be pseudoallergy which had no relation with the activation of complement system.

Adolescent ; Adult ; Animals ; Cell Degranulation ; drug effects ; Cell Line, Tumor ; Chemistry, Pharmaceutical ; Complement System Proteins ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; pharmacology ; Hexosaminidases ; secretion ; Histamine Release ; drug effects ; Humans ; Injections ; Rats ; Young Adult

Ongoing effort to find novel antiasthmatic drugs led to the design and synthesis of a series of compounds bearing phenyl tetrazole group based on the SAR study. The important intermediate 3-(1H-tetrazol-5-yl) benzenamine was synthesized from m-nitroaniline via cyclization and hydrogenation. Followed by amidation, eight new target compounds were obtained. The structures of these compounds were confirmed with 1H NMR, ESI-MS and elemental analysis. Their non-specific and specific anti-histamine effects in the mast cell were determined. Compound NP03 could inhibit non-specific histamine release induced by compound 48/80 in mast cell of SD rats.
Animals ; Anti-Asthmatic Agents ; chemical synthesis ; chemistry ; pharmacology ; Histamine Release ; drug effects ; Mast Cells ; drug effects ; metabolism ; Molecular Structure ; Rats ; Rats, Sprague-Dawley ; Structure-Activity Relationship ; Tetrazoles ; chemical synthesis ; chemistry ; pharmacology ; p-Methoxy-N-methylphenethylamine ; pharmacology

OBJECTIVETo evaluate the effects of Caulis Sinomenii and sinomenine on conditioned place preference (CPP) induced by morphine and brain histamine level in mice.

METHODSSixty mice were randomized into 6 equal groups and morphine (Mor) was injected subcutaneously (9 mg/kg) for 6 consecutive days to induce CPP using a shuttle box. Since the 4th day of training, the mice in 5 of the groups were treated for 3 consecutive days with Caulis Sinomenii (10 g/kg), sinomenine (60 mg/kg), diphenhydramine (30 mg/kg), CP48/80 (5 mg/kg) and L-histidine (750 mg/kg) in addition to morphine (9 mg/kg) treatment, respectively, leaving the other group with exclusive morphine treatment. Another 10 mice received saline injection to serve as saline control group. The content of histamine (HA) in the mouse brain was measured by fluorospectrophotometry.

RESULTSIn morphine group, the mice showed significantly extended stay in morphine-paired compartment whose HA content in the brain was markedly increased (P<0.01). Treatment with Caulis Sinomenii and sinomenine resulted in significantly reduced time of stay in morphine-paired compartment and brain HA level (P<0.01).

CONCLUSIONCPP induced by morphine in mice is associated with increased HA level in the brain. Caulis Sinomenii and sinomenine can suppress the acquisition of place preference induced by morphine and modulate HA level in the central nervous system in morphine-dependent mice.

Animals ; Arginine ; pharmacology ; Brain ; drug effects ; metabolism ; Conditioning, Operant ; drug effects ; physiology ; Diphenhydramine ; pharmacology ; Histamine ; metabolism ; Male ; Mice ; Morphinans ; pharmacology ; Morphine ; toxicity ; Morphine Dependence ; etiology ; physiopathology ; Motor Activity ; drug effects ; Random Allocation ; Sinomenium ; chemistry

OBJECTIVE: The goal of this study was to study the mechanism of substance P (SP)-mediated the neural control of mast cell (MC) degranulation. METHOD: Bone marrow mast cells from mice were cultured with stem cell factor (SCF), IL-3 and IL-4 (group A) and SCF, IL-3 (group B) for four weeks. Then the cells were harvested and reserved for studies. Western Blot hybridization technique was used to detect the expression of FcεR I α and NK-1R on MCs from the two groups. Then such cells were activated with SP (0, 0. 01, 0. 10, 1. 00, 10. 00 µg/ml, respectively) for 30 min. The histamine released into the supernatant and stored in the protoplasm was quantified by enzyme linked immunosorbent assay (ELISA). And the percentage of histamine release was calculated as a percent of total histamine content. RESULT: The expressions of FcεR I α and NK-1R on these mast cells in group A were statistically higher than in group B (P<0. 05). The MCs from two groups can be actived when stimulated by SP, but the level of MC degranulation in group A was higher than group B (P<0. 05). CONCLUSION Neuropeptide may stimulate MC degranulation through immunological and non-immunological pathways. In summary, the current study provides us with better understanding of the mechanism of neuropeptide-controlled MC deranulation, and this should be helpful for the further research involved in the mechanism and treatmemt of airway hyper-reactivity.
Animals ; Bone Marrow Cells ; Cell Degranulation ; Cells, Cultured ; Culture Media ; chemistry ; Histamine ; metabolism ; Interleukin-3 ; pharmacology ; Interleukin-4 ; pharmacology ; Mast Cells ; cytology ; metabolism ; Mice ; Stem Cell Factor ; pharmacology ; Substance P ; pharmacology

OBJECTIVETo study the influence of Xinqin tablets on guinea-pig nasal hypersensitivity.

METHOD2,4-Toluene Diisocyanate (TDI) was selected as antigen and used in nose to establish guinea-pig allergic rhinitis. The effects of Xinqin tablets on symptoms of nasal hypersensitivity in guinea-pigs, histamine content of nasal mucosa and activity of nitric oxide synthase (NOS) were examined.

RESULTXinqin tablets could significantly relieve the pathological symptoms of nasal hypersensitivity in guinea-pig, reduce histamine content of nasal mucosa and inhibit the activity of nitric oxide synthase.

CONCLUSIONXinqin tablets have significant effect on nasal hypersensitivity, and prevent the occurrence of allergic rhinitis.

Animals ; Asarum ; chemistry ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacology ; Guinea Pigs ; Histamine ; metabolism ; Male ; Nasal Mucosa ; drug effects ; metabolism ; pathology ; Nitric Oxide Synthase ; metabolism ; Phytotherapy ; Plants, Medicinal ; chemistry ; Rhinitis, Allergic, Perennial ; chemically induced ; metabolism ; pathology ; Scutellaria ; chemistry ; Toluene 2,4-Diisocyanate

AIMTo search for novel antiasthmatic agents.

METHODSCoupling seratrodast (SD), an antiasthmatic drug, with several different types of NO donors including oxatriazoles, N-hydroxyguanidines and furoxans; evaluating the antiasthmatic effects of coupled compounds by determining their inhibitory activity of guinea pig asthma induced by acetylcholine and histamine; and assessing NO releasing ability.

RESULTSNine novel target compounds (I1-9) were synthesized, and their structures were established by IR, NMR, MS and elemental analysis. Preliminary pharmacological test showed that most of the compounds showed high antiasthmatic activities (the latent period of induced asthma was prolonged from 10 s (SD) to 26-62 s), among which 3 compounds (I4, I6, I7) were more potent than SD (P < 0.05, P < 0.01) and released more NO than others. The maximum concentrations (Cmax) of NO-release in vitro were 0.1878, 0.1393 and 0.2473 mg x L(-1), respectively.

CONCLUSIONNO donating-SD derivatives are worthy to be futher investigated.

Acetylcholine ; Animals ; Anti-Asthmatic Agents ; chemical synthesis ; pharmacology ; therapeutic use ; Asthma ; chemically induced ; prevention & control ; Benzoquinones ; chemical synthesis ; pharmacology ; therapeutic use ; Guanidines ; chemistry ; pharmacology ; Guinea Pigs ; Heptanoic Acids ; chemical synthesis ; pharmacology ; therapeutic use ; Histamine ; Nitric Oxide ; metabolism ; Nitric Oxide Donors ; chemistry ; pharmacology ; Oxadiazoles ; chemistry ; pharmacology ; Structure-Activity Relationship

OBJECTIVETo evaluate the immunoregulatory effects of the Lonicera water extract in the ovalbulmin (OVA)-sensitized BALB/c mice and to explore feasibility of treating food allergy with the traditional Chinese medicine (TCM).

METHODSForty female BALB/c mice aged 6 weeks fed with ovalbulmin-free feed, were randomly divided into 5 groups with 8 mice in each. Four groups were sensitized with OVA intraperitoneally two times and challenged intragastrically four times. Groups H, M and L were treated respectively with high (100 mg/100 ml), medium (50 mg/100ml) and low (25 mg/100 ml) concentration of the Lonicera water extract at a dose of 0.3 ml/10 g body weight just 4 hours after the first challenge and then twice daily for 10 consecutive days. The mice in group Ch were used as positive control and were sensitized intraperitoneally and treated with normal saline solution intragastrically daily. The mice in NS group were used as negative control without sensitization and challenge. Just 1 hour after the last challenge, the mice in each group were sacrificed and specimens of jejunum were taken. Histological examinations on the jejunum specimens were performed after either HE or toluidine blue staining, the levels of histamine in gut of the mice were assayed with a fluorescent method; the IFN-gamma and IL-4 production in peripheral lymph node mononuclear cell (PLNMC) and the OVA-specific IgE levels in serum were measured by using ELISA; the mRNA expression of IL-12p40 in PLNMC of the mice was evaluated by RT-PCR; the footpad swelling reactions were assessed for the OVA-induced delayed hypersensitivity.

RESULTS(1) The inflammatory reactions were significantly inhibited in the mice of group H and M; the accumulated and degranulated mast cells in lamina propria were significantly reduced in the mice by gavage with 100% or 50% of the Lonicera extract, concomitant with the increased percentage of the intact mast cells. (2) The release of histamine in gut in the mice of group H and M was significantly reduced. (3) Either the IL-4 production and the ratio of IL-4/IFN-gamma in PLNMC or the IFN-gamma generation was significantly reduced in group H and M. (4) IL-12p40 mRNA expression in PLNMC was significantly reduced in group H and M. (5) The levels of OVA-specific IgE in serum were reduced in the mice of group H and M. (6) The footpad swelling reactions induced in the allergic mice were significantly inhibited after giving the Lonicera extract of the three different concentrations.

CONCLUSIONThe Lonicera extract showed significant immunoregulatory effects in OVA-induced allergic mice model in this study. Lonicera extract may be of potential research value in treatment of both IgE and none IgE mediated food allergy.

Animals ; Female ; Food Hypersensitivity ; drug therapy ; immunology ; Histamine ; analysis ; Immunoglobulin E ; blood ; Interferon-gamma ; metabolism ; Interleukin-12 Subunit p40 ; analysis ; Interleukin-4 ; metabolism ; Jejunum ; metabolism ; pathology ; Lonicera ; chemistry ; Mast Cells ; immunology ; Mice ; Mice, Inbred BALB C ; Ovalbumin ; administration & dosage ; Plant Extracts ; immunology ; pharmacology