Biomedical subjects

C Kamei

Publications and source records attributed to C Kamei.

At least 37 records · Page 2Linked to original sources

PubMed2000

Vascular permeability in allergic conjunctivitis in mice lacking histamine H1 receptors.

To clarify the role of histamine H1 receptors in allergic conjunctivitis, changes in vascular permeability of the conjunctiva were measured in histamine H1 receptor deficient mice. Wild-type mice showed a significant increase in vascular permeability of the conjunctiva induced by histamine. However, no such increase was found in histamine H1 receptor deficient mice. On the other hand, no differences were observed between wild-type and histamine H1 receptor deficient mice in response to serotonin. A significant increase in vascular permeability was observed in actively sensitized wild-type mice, whereas no increase was observed in histamine H1 receptor deficient mice. Similar findings were noted in passively sensitized animals. Histamine contents of the conjunctiva were significantly decreased by topical application of antigen in both wild-type and histamine H1 receptor deficient mice after active sensitization with antigen. These findings suggested that vascular permeability in the conjunctiva in allergic conjunctivitis is entirely regulated through histamine H1 receptor.

Animals↗

PubMed2000

Effects of metabolic fragments of [Arg(8)]-vasopressin on nerve growth in cultured hippocampal neurons.

The effects of metabolic fragments of [Arg(8)]-vasopressin (AVP), [pGlu(4), Cyt(6)]AVP (AVP(4-9)), and desglycinamide-[pGlu(4), Cyt(6)]AVP (AVP(4-8)) on the growth of hippocampal neurons in culture were investigated in comparison with those of AVP. AVP(4-9) caused a significant increase in filopodial length following 96 h of exposure at concentrations higher than 300 nM. AVP(4-9) was more potent than AVP. AVP(4-8) also induced an increase in filopodial length, but this effect was less than that of AVP. The selective V(1) agonist [Phe(2), Ile(3), Orn(8)]-vasopressin caused a significant increase in filopodial length, whereas the selective V(2) agonist [deamino-Cys(1), D-Arg(8)]-vasopressin showed no such effect. OPC-21268, a vasopressin V(1) antagonist, blocked AVP and AVP fragment-induced increases in filopodial length. However, the V(2) antagonist OPC-31260 showed no such effect. A23187, a representative Ca ionophore, also increased filopodial length, and the A23187-induced increase in filopodial length was potentiated by AVP and AVP fragments. These results indicated that AVP(4-9) and AVP(4-8) increased filopodial length in cultured hippocampal neurons by activating V(1) receptors. Both phenomena induced by AVP(4-9) and AVP(4-8) were associated with intracellular calcium mobilization.

Animals↗

PubMed2000

A new model of allergic rhinitis in rats by topical sensitization and evaluation of H(1)-receptor antagonists.

An animal model of chronic allergic rhinitis was developed by repeated local booster sensitization into the nasal cavity in sensitized rats. The severity of allergic rhinitis was assessed by determining the extent of two markers of nasal allergic symptoms (sneezing and nasal rubbing) after antigen challenge. The number of incidents of sneezing and nasal rubbing was markedly increased during intranasal instillation of antigen in sensitized rats. The PCA titers were also markedly elevated by intranasal sensitization. Some histamine H(1)-receptor antagonists such as chlorpheniramine, ketotifen, astemizole and epinastine inhibited the increase in antigen-induced nasal symptoms in a dose-related manner. Nasal rubbing was more potently inhibited by H(1)-receptor antagonists than sneezing. In conclusion, we developed a chronic allergic rhinitis model showing nasal symptoms in rats, and this model may be useful for evaluating the effects of drugs on allergic rhinitis.

Allergens↗

PubMed2000

Desensitization of beta2-adrenoceptor and hypersensitization to phosphodiesterase inhibitors elicited by beta2-agonists in guinea pig eosinophils.

BACKGROUND: Although the existence of functional beta(2)-adrenoceptor on eosinophils has been reported, the effects of desensitization of beta(2)-adrenoceptors on eosinophils have not been well documented. OBJECTIVE: The effects of desensitization of beta(2)-adrenoceptors on the degranulation of guinea pig eosinophils were investigated. METHODS: Guinea pig eosinophils were stimulated with the calcium ionophore A23187, and eosinophil peroxidase (EPO) release was determined. Changes in intracellular cyclic adenosine monophosphate (cAMP) levels were also measured. RESULTS: A23187-induced EPO release from guinea pig eosinophils was inhibited in a concentration-dependent manner by pretreatment for 5 minutes with fenoterol, clenbuterol, and salbutamol. Such effects of beta(2)-agonists were abolished by pretreatment with KT5720, an inhibitor of protein kinase A. Desensitization of the inhibitory effects of beta(2)-agonists was observed when the incubation time was prolonged. Fenoterol (10(-6) mol/L) induced almost complete desensitization after 120 minutes of incubation, whereas clenbuterol did not bring about significant desensitization. The inhibitory effects of fenoterol and clenbuterol on A23187-induced EPO release were correlated with increases in the intracellular cAMP levels evoked by either compound. After incubation of eosinophils with 10(-6) mol/L fenoterol for 120 minutes to induce complete desensitization of beta(2)-adrenoceptors, the inhibitory effects of theophylline and rolipram were increased by about 100-fold in the desensitized cells, although the effects of forskolin and dibutyryl cAMP were not affected by beta(2)-adrenoceptor desensitization. CONCLUSIONS: Prolonged incubation with beta(2)-agonists induced desensitization of beta(2)-adrenoceptors. Also, we postulated that hypersensitization of phosphodiesterase to its inhibitors occurs in beta(2)-adrenoceptor-desensitized guinea pig eosinophils.

Adrenergic beta-Agonists↗

PubMed2000

Effect of mometasone furoate by topical application on allergic rhinitis model in rats.

The effects of mometasone furoate on experimental allergic rhinitis in rats were studied in comparison with that of fluticasone propionate. Topical application of both drugs inhibited dose-dependently the increase of nasal symptoms (sneezing and nasal rubbing) after antigen challenge to the nasal cavity of actively sensitized rats. Mometasone furoate and fluticasone propionate at concentrations of 0.01 or 0.1% significantly inhibited both nasal rubbing and sneezing 1 h after topical application of both drugs. The relative potencies of mometasone furoate in nasal rubbing and sneezing compared to fluticasone propionate were 5.01 and 6.87, respectively. Mometasone furoate (0.02%) and fluticasone propionate (0.1%) significantly inhibited the increase of antigen-induced nasal rubbing even 6 h after topical application, indicating that both drugs have a long-lasting effect.

Administration, Topical↗

PubMed2000

Effects of fujibitol, a remedy for nasal symptoms, on experimental allergic rhinitis in rats.

The effects of Fujibitol, a preparation of crude drugs in wide clinical use for treatment of chronic rhinitis and empyema, on experimental allergic rhinitis in rats were studied. Fujibitol inhibited nasal allergic symptoms, i.e. sneezing and nasal rubbing, induced by antigen in sensitized animals. An increase in dye leakage into the nasal cavity induced by antigen was also inhibited by Fujibitol. On the other hand, no inhibitory effects were observed on either the nasal allergic symptoms or increase in dye leakage into the nasal cavity induced by histamine. However, Fujibitol was effective in inhibiting histamine release from the nasal cavity induced by antigen. Oxatomide used as positive control drug showed potent inhibitory effects on nasal symptoms and dye leakage into the nasal cavity induced by histamine and antigen. These results suggested that Fujibitol showed a remarkable protective effect against experimental rhinitis induced by antigen via inhibition of histamine release from the nasal cavity.

Animals↗

PubMed2000

Experimental allergic conjunctivitis in guinea pigs induced by Japanese cedar pollen.

We report a new experimental allergic conjunctivitis with Japanese cedar pollen as antigen in guinea pigs, and the immunological characteristics of this model were also elucidated. Allergic conjunctivitis was developed by immunization in guinea pigs with a mixture containing Japanese cedar pollen and killed Bordetella pertussis. When local application of Japanese cedar pollen suspension 14 d after systemic immunization was performed every 3d, remarkable conjunctivitis was observed from 20 to 35 d. Increase in vascular permeability and decrease in histamine contents of the conjunctiva were also observed after local application of antigen. Passive cutaneous anaphylactic (PCA) reactions revealed that both IgG- and IgE-rich antibodies were produced in this model. Chlorpheniramine, ketotifen and levocabastine were effective in inhibiting cedar pollen-induced conjunctivitis. Although a high concentration was needed, tranilast and amlexanox also showed significant inhibition of conjunctivitis induced by cedar pollen.

Animals↗

PubMed2000

Preparation and characterization of two crystalline forms of 4-amino-5-chloro-2-methoxy-N-[(2S,4S)-1-ethyl-2-hydroxymethyl-4-pyrroli dinyl]benzamide (TKS159).

For 4-amino-5-chloro-2-methoxy-N-[(2S,4S)-1-ethyl-2-hydroxymethyl-4-pyrrolid inyl]benzamide (TKS159), two polymorphs, forms alpha and beta, were prepared and characterized by means of X-ray powder diffractometry, thermal analysis, infrared spectroscopy and 13C-NMR spectroscopy, both in the solution and solid phases. The X-ray powder diffraction analysis gave different patterns for forms alpha and beta. In the thermogravimetry and differential thermal analysis profiles, form beta exhibited characteristic endo- and exothermic peaks at 112.7 degrees C and 116.2 degrees C, respectively, due to the partial melting-induced phase transition to form alpha without accompanying weight loss, and these were followed by an additional endothermic peak at 138.2 degrees C due to fusion. For form alpha, only an endothermic peak at 137.8 degrees C due to fusion was observed. The IR spectroscopic analyses of forms alpha and beta gave different absorption bands assigned to N-H and O-H stretching, N-H bending, and C=O stretching vibrations. From the data obtained by thermal analysis, form alpha was shown to be thermodynamically more stable than form beta.

Benzamides↗

PubMed2000

Participation of GABAergic and histaminergic systems in inhibiting amygdaloid kindled seizures.

The effects of GABAmimetic drugs on inhibition of amygdaloid kindled seizures induced by clobenpropit were investigated to clarify the relationship between histaminergic and GABAergic systems in seizures. I.p. injection of clobenpropit caused dose-dependent inhibition of amygdaloid kindled seizures. GABAmimetic drugs such as diazepam, sodium valproate and muscimol also inhibited amygdaloid kindled seizures in a dose-dependent manner. Diazepam at doses of 0.2 and 0.5 mg/kg, which showed no significant effect on amygdaloid kindled seizures when used separately, significantly potentiated the effect of clobenpropit. Similar findings were observed with sodium valproate and muscimol at doses of 100 mg/kg and 5 ng, respectively, although neither showed any significant effects when administered separately. Bicuculline caused significant antagonism of the inhibition of amygdaloid kindled seizures induced by clobenpropit, while the effect of diazepam was not antagonized by diphenhydramine. These results suggested that inhibition of amygdaloid kindled seizures induced by histamine is closely associated with the actions of GABA.

Amygdala↗

PubMed2000

Regulatory mechanism of eosinophil peroxidase release from guinea pig eosinophils.

The regulatory mechanism of degranulation of guinea pig peritoneal eosinophils was studied by determination of eosinophil peroxidase (EPO) release. Beta-agonists, such as isoproterenol, salbutamol and fenoterol, effectively inhibited A23187-induced EPO release from guinea pig eosinophils. The inhibitory effects of beta-agonists were attenuated by pretreatment with either propranolol, a non-selective beta-antagonist, or ICI 118,551, a selective beta2-antagonist. Both theophylline and dibutyryl-cAMP (db-cAMP) also significantly inhibited A23187-induced EPO release. The inhibition of EPO release induced by db-cAMP was attenuated by pretreatment with KT5720, a protein kinase A inhibitor. In addition, calphostin C as well as cytochalasin D effectively inhibited A23187-induced EPO release. From the results of the present study, it was concluded that an increase in intracellular Ca2+ concentration may lead to exocytosis of eosinophil granules through activation of protein kinase C and microfilaments. Beta-agonists and theophylline were effective in inhibiting degranulation of eosinophils by increasing intracellular cAMP level coupled with the activation of protein kinase A.

Adrenergic beta-Agonists↗

PubMed2000

Influences of everninomicin, vancomycin and teicoplanin on chemical mediator release from rat peritoneal mast cells.

We examined influences of certain antibiotics on the release of chemical mediators from isolated rat peritoneal mast cells in vitro. Isolated peritoneal mast cells were obtained from male Wistar strain rats. Everninomicin (0.06-1.2 mg/ml), vancomycin (0.05-1.0 mg/ml), teicoplanin (0.07-1.4 mg/ml) and concanavalin A (0.01 mg/ml) were used. Isolated mast cells were incubated in the presence of various concentrations of the test compound at 37 degrees C for 10 min. Histamine contents of the supernatant and cell pellet were measured by an automated fluorometric method. Prostaglandin D2 (PGD2) contents of the supernatant were determined by enzyme immunoassay. Everninomicin (0.06-1.2 mg/ml) had no influence on histamine and PGD2 release from mast cells. On the other hand, vancomycin significantly released both histamine (0.5 and 1.0 mg/ml) and PGD2 (1.0 mg/ml) from mast cells, but vancomycin did not affect concanavalin A-induced histamine and PGD2 release. Teicoplanin (more than 0.07 mg/ml) significantly stimulated histamine and PGD2 release from mast cells and it also significantly potentiated concanavalin A-induced histamine and PGD2 release. These results suggest that everninomicin causes no chemical mediator release from mast cells, different from vancomycin and teicoplanin.

Aminoglycosides↗

PubMed2000

The mechanism responsible for the drowsiness caused by first generation H1 antagonists on the EEG pattern.

The present study was performed to clarify the mechanism responsible for the drowsiness caused by first generation H1 antagonists according to electroencephalogram activity. All H1 antagonists used in the present study caused the EEG-recorded drowsiness pattern, i.e., increases in EEG power spectra of the delta and theta bands at the frontal cortex in rats. The potency of cyproheptadine was greater than those of diphenhydramine and promethazine, while that of pyrilamine was less than those of the other drugs examined. The increase in EEG power spectra in the delta band induced by H1 antagonists was antagonized by pretreatment with both histidine and physostigmine. The effect of pyrilamine was more potently antagonized by histidine and less potently antagonized by physostigmine as compared to diphenhydramine, promethazine and cyproheptadine. The increases in EEG power spectra induced by H1 antagonists were neither antagonized nor potentiated by 5-hydroxytryptophan. These results clearly indicate that the increases in EEG power spectra in the delta and theta bands at the frontal cortex in rats induced by first generation H1 antagonists are responsible for both histaminergic and cholinergic mechanisms.

5-Hydroxytryptophan↗

PubMed2000

Facilitating effects of histamine on spatial memory deficit induced by scopolamine in rats.

AIM: To investigate whether or not histamine was involved in scopolamine-induced spatial memory deficits evaluated in 8-arm radial maze performance of rats. METHODS: Eight-Arm radial maze performance was used to measure spatial memory in rats, and the brain regions were subsequently dissected and histamine contents were determined by HPLC. RESULTS: Intracerebroventricular (icv) injection of histamine (100 or 200 ng) or thioperamide (50 micrograms), and intraperitoneal (i.p.) injection of histidine (1000 mg/kg) ameliorated memory impairment induced by scopolamine regarding both parameters of radial maze performance. 2-Thiazolylethylamine, but not 4-methylhistamine showed the similar effect to histamine. Both histamine (200 ng, icv) and histidine (1000 mg/kg, i.p.) were equally effective in increasing the histamine content in the cortex, hippocampus, and hypothalamus. CONCLUSION: These results suggest that brain histamine plays an important role in learning and memory, and its action may be due to cholinergic neurons.

Animals↗

PubMed1999

Effects of histamine on MK-801-induced memory deficits in radial maze performance in rats.

The effects of histamine on the spatial memory deficits induced by MK-801 were investigated using the eight-arm radial maze paradigm in rats. Intracerebroventricular (i.c.v.) injection of histamine or thioperamide, and intraperitoneal (i.p.) injection of histidine improved the spatial memory deficits induced by MK-801. Similar results were obtained with 2-thiazolylethylamine. In contrast, 4-methylhistamine showed no significant effect. Based on these observations, it seems likely that the protective effect of histamine on MK-801-induced spatial memory deficit is mediated by H(1)-receptors.

Analysis of Variance↗

PubMed1999

[Arg8]-vasopressin-induced increase in intracellular Ca2+ concentration in cultured rat hippocampal neurons.

Changes in intracellular Ca2+ concentration ([Ca2+]i) induced by [Arg8]-vasopressin (AVP) were studied in cultured rat hippocampal neurons by fura-2 fluorometry. AVP (10-1,000 nM) caused a dose-dependent increase in [Ca2+]i. The selective V1 vasopressin receptor agonist [Phe2, Ile3, Orn8]-vasopressin also induced a significant increase in [Ca2+]i, whereas the selective V2 vasopressin receptor agonist [deamino Cys1, D-Arg8]-vasopressin showed no effect. The AVP-induced increase in [Ca2+]i was inhibited by the selective V1 vasopressin receptor antagonist d(CH2)5[Tyr2(Me), Arg8]-vasopressin and nonpeptide V1 antagonist OPC-21268. On the other hand, no antagonistic effects were observed with the V2 vasopressin antagonist desglycinamide-[d(CH2)5, D-Ile2, Ile4, Arg8]-vasopressin and nonpeptide V2 antagonist OPC-31260. The increase in [Ca2+]i induced by AVP was abolished after removal of extracellular Ca2+. In addition, AVP-induced [Ca2+]i elevation was not affected by treatment with verapamil, which blocked the [Ca2+]i increase induced by an isotonic high K(+)-medium (50 mM). However, omega-conotoxin GVIA completely inhibited the effect of AVP. These results suggested that the AVP-induced [Ca2+]i increase in cultured rat hippocampal neurons is due to influx of Ca2+ through V1 VP receptors coupled with N-type calcium channels.

Animals↗

PubMed1999

Effects of intracerebroventricular injection of alpha-fluoromethylhistidine on radial maze performance in rats.

The effects of alpha-fluoromethylhistidine (alpha-FMH) on spatial cognition were investigated using the eight-arm radial maze paradigm in rats. Intracerebroventricular (ICV) injection of alpha-FMH resulted in spatial memory deficits characterized by an increase in the number of total errors (TE) and a decrease in the number of initial correct responses (ICR). There was a strong correlation between increases in the number of TE and decreases in histamine contents of the cortex and hippocampus regions of the brain, which are known to participate in learning and memory. On the other hand, both histamine (50-100 ng, ICV) and thioperamide (10 microg, ICV) significantly ameliorated the memory deficit induced by alpha-FMH. However, metoprine showed no significant effect on the alpha-FMH-induced memory deficit. Pyrilamine and R-(alpha)-methylhistamine enhanced the memory deficit induced by alpha-FMH, at doses that had no appreciable effect when administered alone. In contrast, no significant influence on alpha-FMH-induced memory deficit was observed with zolantidine.

Animals↗

PubMed1999

Ultraviolet B (UVB) light-induced histamine release from rat peritoneal mast cells and its augmentation by certain phenothiazine compounds.

When rat peritoneal mast cells were exposed to ultraviolet (UV) light (UVA, UVB and UVC), histamine release was evoked in a dose (intensity X time) dependent manner. The potency order of UV light in inducing the histamine release was UVC > UVB >> UVA. In this study, we focused on the effect of ultraviolet B (UVB) on histamine release from rat mast cells. The UVB-induced histamine release occurred at doses higher than 7.8 kJ m(-2), even at 4 degrees C. At a UVB dose of 18.8 kJ m(-2), where a 51.9+/-4.8% histamine release and a 58.8+/-6.8% degranulation took place, Trypan blue-stained cells accounted for 14.4+/-1.3% of the cells, and the lactate dehydrogenase (LDH) release was about 4.9+/-2.8%. This suggests that the membrane permeability to low molecular weight substances was increased by UVB exposure. The UVB-induced histamine release was inhibited by ascorbic acid at concentrations higher than 500 microM, suggesting the involvement of a radical reaction in the process. The UVB-induced histamine release was enhanced by some phenothiazine compounds, i.e., promethazine, trimeprazine, mequitazine, chlorpromazine, trifluoperazine, ethopropazine and thioridazine. We conclude that the phototoxicity of phenothiazine compounds may be due in part to an enhancement of UVB-induced histamine release from mast cells.

Adjuvants, Immunologic↗

PubMed1999

Slow wave sleep-inducing effects of first generation H1-antagonists.

The present study was performed to see if first-generation histamine H1-antagonists are useful sedative-hypnotic drugs. Increases in electroencephalogram (EEG) power spectra of the delta band (0-4 Hz) at the frontal cortex and theta band (4-8 Hz) at the hippocampus in rats were used as an indexes of sleep. The H1-antagonists used in this study resulted in a decrease in sleep latency and an increase in sleep duration (slow wave sleep). The rate of REM (rapid eye movement) sleep during slow wave sleep was decreased by H1-antagonists and brotizolam. The order of potency of H1-antagonists for the reduction in sleep latency (from greatest to least) was promethazine>chlorpheniramine>diphenhydramine and pyrilamine, and that for the increase in sleep duration was chlorpheniramine>promethazine>diphenhydramine and pyrilamine. Brotizolam was more potent than these H1-antagonists, with 14-18-fold and 4-14-fold greater effects on sleep latency and duration, respectively. These results clearly show that H1-antagonists are effective in mild to moderate insomnia as sedative-hypnotic drugs.

Animals↗