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C Kamei

Publications and source records attributed to C Kamei.

At least 19 recordsLinked to original sources

How best to fight that nasty itch - from new insights into the neuroimmunological, neuroendocrine, and neurophysiological bases of pruritus to novel therapeutic approaches.

While the enormous clinical and psychosocial importance of pruritus in many areas of medicine and the detrimental effects of chronic 'itch' on the quality of life of an affected individual are widely appreciated, the complexity of this sensation is still often grossly underestimated. The current Controversies feature highlights this complexity by portraying pruritus as a truly interdisciplinary problem at the crossroads of neurophysiology, neuroimmunology, neuropharmacology, protease research, internal medicine, and dermatology, which is combated most successfully if one keeps the multilayered nature of 'itch' in mind and adopts a holistic treatment approach - beyond the customary, frequently frustrane monotherapy with histamine receptor antagonists. In view of the often unsatisfactory, unidimensional, and altogether rather crude standard instruments for pruritus management that we still tend to use in clinical practice today, an interdisciplinary team of pruritus experts here critically examines recent progress in pruritus research that future itch management must take into consideration. Focusing on new insights into the neuroimmunological, neuroendocrine, and neurophysiological bases of pruritus, and discussing available neuropharmacological tools, specific research avenues are highlighted, whose pursuit promises to lead to novel, and hopefully more effective, forms of pruritus management.

Dermatology↗

Effect of paroxetine on marble-burying behavior in mice.

The present study was undertaken to investigate the effect of paroxetine, a selective serotonin reuptake inhibitor (SSRI), on marble-burying behavior in mice in comparison with those of fluvoxamine and clomipramine. Marble-burying test is extensively used as an animal model for obsessive/compulsive disorder. A significant inhibition in marble-burying behavior was observed with paroxetine, at a dose of 10 mg/kg. The earlier SSRI, fluvoxamine, also significantly inhibited marble-burying behavior at a dose of 30 mg/kg. Although clomipramine, a tricyclic antidepressant, caused an inhibition in marble-burying behavior, a high dose of 100 mg/kg was needed to show a significant effect. On the other hand, all the drugs used in the present study showed no significant changes in spontaneous locomotor activity at doses inhibiting marble-burying behavior. In conclusion, it was confirmed that paroxetine has a potent inhibitory effect on marble-burying behavior in mice, and could have a similar antiobsessive/anticompulsive activity in human beings.

Animals↗

Pruritus-associated response mediated by cutaneous histamine H3 receptors.

BACKGROUND: Histamine is one of the most common chemical mediators causing pruritus, and H1 receptor antagonists have been used as a first choice in its treatment. On the other hand, although the presence of H3 receptors has been identified in the skin, few studies have investigated the involvement of H3 receptors on pruritus. OBJECTIVE: The purpose of this study was to examine whether H3 receptor agonist or antagonist influences the incidence of scratching behaviour in ICR or mast cell-deficient WBB6F1-W/WV mice. METHODS: The mice were given an intradermal injection of H3 receptor agonist or antagonist into the rostral part of the back, and the occurrence of scratching behaviour at the injected site by the hind paws was counted over 60 min. RESULTS: H3 receptor antagonists, thioperamide and AQ0145 significantly increased the incidence of scratching behaviour in ICR mice. H3 receptor agonist, (R)-alpha-methylhistamine, had no effect. On the other hand, (R)-alpha-methylhistamine significantly inhibited thioperamide or AQ0145-induced scratching behaviour. In addition, both thioperamide and AQ0145 elicited scratching behaviour in mast cell-deficient WBB6F1-W/WV mice. CONCLUSION: From these results, it may be concluded that H3 receptors are involved in the modulation of pruritus in the skin, and mast cells are not essential in this response. In addition, H3 receptor agonists can be useful as a novel therapeutic approach against pruritus.

Adamantane↗

Intracerebroventricular administration of histamine H3 receptor antagonists decreases seizures in rat models of epilepsia.

The effects of histamine H3 antagonists on amygdaloid kindled and maximal electroshock seizures in rats were studied to determine their potential as new antiepileptic drugs. Under pentobarbital anesthesia, rats were fixed to a stereotaxic apparatus and a stainless steel guide cannula for drug administration was implanted into the lateral ventricle. In amygdaloid kindled seizures, electrodes were implanted into the right amygdala and electroencephalogram was recorded bipolarly; stimulation was applied bipolarly every day by a constant current stimulator and continued until a generalized convulsion was obtained. In the maximal electroshock (MES) seizure test, electroconvulsion was induced by stimulating animals through ear-clip electrodes, and the durations of tonic and clonic seizures were measured. Thioperamide, clobenpropit, iodophenpropit, VUF5514, VUF5515 and VUF4929 caused a dose-dependent inhibition of both seizure stage and afterdischarge (AD) duration of amygdaloid kindled seizures. The duration of tonic seizure induced by MES was also inhibited by H3 antagonists, but the duration of clonic seizures were unchanged. Among the H3 antagonists tested, clobenpropit and iodophenpropit were somewhat more potent than the other drugs on amygdaloid kindled seizures and MES seizures, respectively. These results indicate that some H3 antagonists may be useful as antiepileptic drugs, especially for secondary generalized seizures and/or tonic-clonic seizures in humans.

Amygdala↗

Involvement of histamine H3 receptors in scratching behaviour in mast cell-deficient mice.

BACKGROUND: Although the roles of histamine H3 receptors have been studied in several tissues such as the brain, lung, spleen, colon and peripheral sensory nerve endings, the involvement of H3 receptors in skin responses particularly in relation to scratching behaviour are not well documented. OBJECTIVES: This work was performed to study the effects of histamine H3 antagonists on scratching behaviour in mast cell-deficient mice. METHODS: Histamine H3 antagonists iodophenpropit and clobenpropit, histamine and substance P were injected intradermally into the rostral part of the back of mast cell-deficient (WBB6F1 W/Wv) and wild-type (WBB6F1+/+) mice and scratching behaviour was measured for 60 min. The effects of H1 antagonists on scratching behaviour induced by H3 antagonists were also investigated. RESULTS: Intradermal injection of iodophenpropit and clobenpropit at doses of 10 and 100 nmol per site caused significant increases in scratching behaviour in both mast cell-deficient and wild-type mice. Histamine also caused a dose-related increase in the incidence of scratching behaviour, and a significant effect was observed at a dose of 100 nmol per site in both mast cell-deficient and wild-type mice. Substance P was also effective in causing scratching behaviour in both mast cell-deficient and wild-type mice. However, histamine H1 antagonists diphenhydramine and chlorphenamine failed to inhibit H3 antagonist-induced scratching behaviour in both types of mice. CONCLUSIONS: Our results indicated that intradermal injection of H3 antagonists induces scratching behaviour and that chemical mediators other than histamine seem to be involved in the response.

Animals↗

Effects of [Arg8]-vasopressin on regional cerebral blood flow in spontaneously hypertensive rats.

The effects of [Arg(8)]-vasopressin (AVP) and related compounds on regional cerebral blood flow (rCBF) in the hippocampus were studied using conscious spontaneously hypertensive rats (SHR). rCBF in the hippocampus decreased gradually with age in proportion to an increase in mean blood pressure. Subcutaneous injection of AVP caused a dose-dependent increase in rCBF in the hippocampus. The effects of the metabolic fragments AVP4-9 and AVP4-8 on rCBF were relatively weak. OPC-31260, a vasopressin V(2) antagonist, antagonized the AVP-induced increase in rCBF in the hippocampus. Furthermore, subcutaneous injection of DDAVP, a V(2) agonist, increased rCBF in the hippocampus. On the other hand, the AVP-induced increase in rCBF in the hippocampus was not antagonized by OPC-21268, a vasopressin V(1) antagonist. Intracerebroventricular injection of AVP caused no significant changes in rCBF in the hippocampus, even at a dose of 10 ng/site.

Animals↗

Role of Src in hypersensitization to phosphodiesterase inhibitors in beta2-adrenoceptor-desensitized eosinophils.

When guinea pig eosinophils were incubated with fenoterol, a beta2-agonist, for 120 min, not only desensitization of beta2-adrenoceptors but also hyperresponsiveness to phosphodiesterase (PDE) inhibitors, such as theophylline and rolipram, was observed. The fenoterol-induced beta2-adrenoceptor desensitization was not affected by pretreatment with either genistein, a broad-spectrum tyrosine kinase inhibitor, or PP2, a specific Src family tyrosine kinase inhibitor. On the other hand, both genistein and PP2 abolished the hyperresponsiveness to PDE inhibitors in beta2-adrenoceptor-desensitized eosinophils. These findings suggested that Src family tyrosine kinases play important roles in the hypersensitization of PDE to PDE inhibitors in beta2-adrenoceptor-desensitized eosinophils.

Adrenergic beta-Agonists↗

Changes in membrane potential induced by compound 48/80 in the peritoneal mast cells of rats.

The changes in membrane potential induced by compound 48/80 were studied using rat peritoneal mast cells. The mean resting membrane potential of rat mast cells was -12.3 +/- 0.7 mM. When compound 48/80 was added to the mast cells, the cells were degranulated approximately 120 sec after the addition of the drug, after which immediate depolarization occurred. Degranulation of mast cells was not observed, even under the depolarization or hyperpolarization conditions caused by the replacement of a high K+ medium or the removal of K+ from the medium, respectively. Under both conditions, when compound 48/80 was added to the mast cells, degranulation was observed. Abrupt and marked depolarization was induced 30-60 sec after compound 48/80 was added. In addition, repolarization followed by gradual depolarization was observed without degranulation in mast cells treated with cytochalasin D after the addition of compound 48/80. These results suggest that the mast cells were depolarized by compound 48/80 independently of degranulation. It is also feasible that the gradual depolarization and repolarization induced by compound 48/80 in mast cells pretreated with cytochalasin D participated in the extracellular Na+ and Na+/K(+)-pump, respectively.

Animals↗

Involvement of central histamine in amygdaloid kindled seizures in rats.

The involvement of central histamine in amygdaloid kindled seizures in rats was investigated using histamine-related compounds. Histamine contents in the amygdala of electrical stimulation site was significantly decreased after development of amygdaloid kindling. Intracerebroventricular (i.c.v.) injection of histamine resulted in inhibition of amygdaloid kindled seizures. The H(1)-agonists 2-methylhistamine and 2-thiazolylethylamine also inhibited amygdaloid kindled seizures. In addition, intraperitoneal (i.p.) injection of histidine and metoprine inhibited amygdaloid kindled seizures at doses that caused increases in histamine contents of the brain. H(1)-antagonists (diphenhydramine and chlorpheniramine) attenuated histamine (i.c.v.)-induced inhibition of amygdaloid kindled seizures, however, no significant antagonism was observed with H(2)-antagonists (cimetidine, ranitidine or zolantidine). Intracerebroventricular injection of H(3)-antagonists (thioperamide and AQ 0145) resulted in a dose-related inhibition of amygdaloid kindled seizures. The same findings were observed when thioperamide and clobenpropit were injected i.p. The effects of thioperamide (i.p.) and AQ 0145 (i.p.) were inhibited by an H(3)-agonist [(R)-alpha-methylhistamine] and H(1)-antagonists (diphenhydramine and chlorpheniramine). On the other hand, H(2)-antagonists (cimetidine and ranitidine) showed no antagonistic effects. These findings suggested that a histaminergic mechanism plays an important role in suppressing amygdaloid kindled seizures through histamine H(1)-receptors.

Amygdala↗

Effects of vasopressin on histamine H(1) receptor antagonist-induced spatial memory deficits in rats.

The effects of [Arg(8)] vasopressin on histamine H(1) receptor antagonist-induced memory deficits were investigated using the eight-arm radial maze performance test in rats. Pyrilamine and diphenhydramine as well as scopolamine induced memory deficits characterized by increases in the number of total errors, reference memory errors and working memory errors. [Arg(8)] vasopressin improved not only scopolamine--but also pyrilamine--and diphenhydramine-induced memory deficits, although a high dose of [Arg(8)] vasopressin was needed to antagonize pyrilamine-induced memory deficits. The effects of pyrilamine on the brain [Arg(8)] vasopressin content were studied, and the hippocampus [Arg(8)] vasopressin content was shown to be decreased after pyrilamine injection. From these observations, it seems likely that [Arg(8)] vasopressin participates in not only the cholinergic system but also the histaminergic system in spatial memory.

Animals↗

Mechanism of the inhibitory effect of histamine on amygdaloid-kindled seizures in rats.

PURPOSE: The mechanism of the inhibitory effect of histamine on amygdaloid-kindled seizures was investigated in rats. METHODS: Under pentobarbital anesthesia, rats were fixed to a stereotaxic apparatus, and bipolar electrodes were implanted into the right amygdala. A guide cannula made of stainless steel tubing was implanted into the right lateral ventricle. Electrodes were connected to a miniature receptacle, which was embedded in the skull with dental cement. EEG was recorded with an electroencephalograph; stimulation of the amygdala was applied bipolarly every day by a constant-current stimulator and continued until a generalized convulsion was obtained. RESULTS: Intracerebroventricular (i.c.v.) injection of histamine at doses of 2-10 microg resulted in a dose-related inhibition of amygdaloid-kindled seizures. I.c.v. injection of calcium chloride at doses of 10-50 microg and A23187 at doses of 2-10 microg also caused dose-dependent inhibition of amygdaloid-kindled seizures. Calcium chloride at a dose of 10 microg, which showed no significant effect on amygdaloid-kindled seizures when used alone, significantly potentiated the effect of histamine. Similar findings were observed with A23187 at a dose of 2 microg. In addition, EGTA and EGTA/AM antagonized the inhibition of kindled seizures induced by histamine. Moreover, the inhibition of kindled seizures induced by histamine was antagonized by KN62. However, calphostin C did not antagonize the inhibitory effect of histamine. CONCLUSIONS: These results indicated that histamine-induced inhibition of amygdaloid-kindled seizures may be closely associated with a calcium calmodulin-dependent protein kinase II activation pathway.

Amygdala↗

Effects of peppermint (Mentha piperita L.) extracts on experimental allergic rhinitis in rats.

The present study was carried out to clarify the effects of extracts of the leaves of Mentha piperita L. on experimental allergic rhinitis. The 50% EtOH extract of peppermint inhibited histamine release from rat peritoneal mast cells induced by compound 48/80. The effect was dose-dependent and significant inhibition was observed at a concentration of 3 microg/ml. In addition, the 50% EtOH eluate separated from the 50% EtOH extract of peppermint by column chromatography (DIAION HP-20) was also effective in inhibiting histamine release at a concentration of 1 microg/ml. Nasal symptoms, sneezing and nasal rubbing induced by antigen challenge in actively sensitized rats were inhibited by oral administration of the 50% EtOH eluate. Significant inhibition of sneezing and nasal rubbing was observed at doses of 300 and 1000 mg/kg, p.o., respectively. Furthermore, the 50% EtOH eluate inhibited dye leakage into the nasal cavity of rats induced by antigen in a dose-dependent manner. These results suggested that extracts of Mentha piperita L. may be clinically effective in alleviating the nasal symptoms of allergic rhinitis.

Animals↗

[Role of central histamine in amygdaloid kindled seizures].

The role of central histamine in amygdaloid kindled seizures in rats was studied. Histamine content in the amygdala was significantly decreased after development of amygdaloid kindling. Intracerebroventricular (i.c.v.) injection of histamine resulted in inhibition of amygdaloid kindled seizures. The H1-agonists 2-methylhistamine and 2-thiazolylethylamine also inhibited amygdaloid kindled seizures. In addition, intraperitoneal (i.p.) injection of histidine and metoprine inhibited amygdaloid kindled seizures at doses that caused increases in histamine contents of the brain. H1-antagonists (diphenhydramine and chlorpheniramine) attenuated histamine- or histidine-induced inhibition of amygdaloid kindled seizures. Both i.c.v. and i.p. injections of H3-antagonists (thioperamide, AQ0145 and clobenpropit) resulted in a dose-related inhibition of amygdaloid kindled seizures. The effects of thioperamide and AQ0145 were inhibited by an H3-agonist (R)-alpha-methylhistamine and H1-antagonists. On the other hand, H2-antagonists showed no antagonistic effect. GABAmimetic drugs, diazepam, sodium valproate and muscimol potentiated the effect of clobenpropit. Bicuculline caused significant antagonism of the inhibition of amygdaloid kindled seizures induced by clobenpropit. These findings suggested that a histaminergic mechanism plays an important role in suppressing amygdaloid kindled seizures through histamine H1-receptors. In addition, an inhibition of amygdaloid kindled seizures induced by histamine is closely related with the action of GABA.

Amygdala↗

Effects of histidine on working memory deficits induced by the 5-HT1A-receptor agonist 8-OH-DPAT.

We investigated the effects of histidine on spatial memory deficits induced by the 5-HT1A-receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Working memory deficits were elicited by 8-OH-DPAT without affecting reference memory. Histidine improved the working memory deficit induced by 8-OH-DPAT at doses causing a significant increase in brain histamine content. This finding suggests that the histaminergic system regulates 8-OH-DPAT-induced working memory deficit.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

The influence of the protein kinase A system in differentiation of HL-60-Eo cells to eosinophils induced by histamine.

The influence of the protein kinase A (A kinase) system in differentiation of HL-60-Eo cells to eosinophils induced by histamine was studied. Although 8-Cl-cAMP caused inhibitions of proliferation and [3H]thymidine uptake of HL-60-Eo cells similarly to histamine, no significant eosinophilic differentiation was observed. Histamine as well as 8-Cl-cAMP caused elevation of A kinase activity. However, KT-5720, an inhibitor of A kinase, had no effect on histamine-induced eosinophil differentiation. RIalpha antisense oligodeoxynucleotide caused significant inhibition of HL-60-Eo cell growth, but RIIbeta antisense oligodeoxynucleotide had no effect. On the other hand, neither of the antisense oligodeoxynucleotides showed potentiating effects on growth inhibition induced by histamine. In addition, RIalpha and RIIbeta antisense oligodeoxynucleotides caused neither differentiation to eosinophils itself nor potentiation of histamine-induced differentiation. From these findings, it was concluded that A kinase is not correlated directly with differentiation of HL-60-Eo cells to eosinophils.

8-Bromo Cyclic Adenosine Monophosphate↗

Effects of histamine and related compounds on the differentiation of HL-60-Eo cells into eosinophils.

The effects of histamine and related compounds on the differentiation of HL-60-Eo cells into eosinophils were studied. The histamine and H2 agonists impromidine and 4-methylhistamine caused concentration-related increases in the number of differentiated cells. On the other hand, the H1 agonists 2-methylhistamine and 2-pyndylethylamine showed no such effect. Histamine-induced eosinophil differentiation was antagonized by the H2 antagonists cimetidine and ranitidine. Histamine and H2 agonists inhibited (3H)-thymidine uptake, suggesting that these compounds caused a decrease in proliferation. Histamine as well as the H2 agonists impromidine and 4-methythistamine caused increases in cAMP level, and this effect was antagonized by ranitidine. From these findings, we concluded that both the differentiation of HL-60-Eo cells into eosinophils and proliferation of HL-60-Eo cells were mediated via H2 receptors.

Cell Differentiation↗

Effect of H1-antagonists on spatial memory deficit evaluated by 8-arm radial maze in rats.

AIM: To evaluate effects of certain H1-antagonists on spatial memory with 8-arm radial maze performance of rats. METHODS: Eight-arm radial maze performance was used to measure spatial memory in rats. RESULTS: Chronic treatments of classical H1-antagonists, diphenhydramine (5 mg/kg) and pyrilamine (20 mg/kg) impaired acquisition memory process regarding both parameters of radial maze performance. In addition, the memory retrieval process was also impaired significantly by a single administration of diphenhydramine (5, 10 mg/kg) and pyrilamine (50 mg/kg). However, the newly developed H1-antagonist, epinastine caused no appreciable effect on both acquisition and retrieval memory even at a high dose of 50 mg/kg. The memory deficit induced by diphenhydramine (10 mg/kg) or pyrilamine (50 mg/kg) was reversed by tacrine (1 mg/kg). CONCLUSION: Histamine H(1)-receptors plays a certain role in spatial cognition, and its action may be due to both histaminergic and cholinergic neurons.

Animals↗

Mechanism responsible for epileptogenic activity by first-generation H1-antagonists in rats.

In the present study, we have demonstrated that multiple first-generation H1-antagonists caused behavioral and EEG seizures in rats. The epileptogenic property of pyrilamine was more potent than either chlorpheniramine or diphenhydramine. In contrast, the second-generation H1-antagonists, loratadine and ebastine did not induce detectable epileptogenic activity. Intraperitoneal injection of histidine inhibited the EEG seizures induced by pyrilamine, diphenhydramine or chlorpheniramine; however no antagonism was observed with physostigmine. These results clearly suggest that the epileptogenic activity of first-generation H1-antagonists is dependent upon a centrally acting histaminergic mechanism.

Animals↗