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Biomedical subjects

A Yamatodani

Publications and source records attributed to A Yamatodani.

At least 19 recordsLinked to original sources
PubMed1998

In vivo modulation of rat hypothalamic histamine release by the histamine H3 receptor ligands, immepip and clobenpropit. Effects of intrahypothalamic and peripheral application.

We investigated the effect of the new potent and selective histamine H3 receptor agonist, immepip, and the histamine H3 receptor antagonist, clobenpropit, on in vivo neuronal histamine release from the anterior hypothalamic area of urethane-anesthetized rats, using microdialysis. Intrahypothalamic perfusion with immepip at concentrations of 1 and 10 nM reduced histamine release to 75% and 35% of its basal level, respectively. Peripheral injection of immepip (5 mg/kg) caused a sustained decrease in histamine release of 50%. Clobenpropit potently increased histamine release after intrahypothalamic perfusion. The maximal increase in histamine release was 2-fold, observed at a concentration of 10 nM clobenpropit. Peripheral injection of clobenpropit (5-15 mg/kg) increased histamine release to about 150% of the basal value. A more marked increase in histamine release was found after injection of the histamine H3 receptor antagonist, thioperamide (5 mg/kg). In conclusion, intrahypothalamic perfusion of the histamine H3 receptor agonist, immepip and the histamine H3 receptor antagonist, clobenpropit, potently and oppositely modulated in vivo histamine release from the anterior hypothalamic area. The decreased histamine release after peripheral injection of immepip indicates that this novel agonist readily crosses the blood-brain barrier, making it a potential candidate for in vivo histamine H3 receptor studies. The differential increase in histamine release after peripheral injection of clobenpropit and thioperamide is discussed.

Animals↗
PubMed1998

Neurological function after deep hypothermic circulatory arrest in the rat.

BACKGROUND: Integrated neurological function, behavior, and somatic recovery were studied in 35 rats undergoing 5 to 80 minutes of hypothermic circulatory arrest (HCA). METHODS AND RESULTS: A closed extracorporeal circulation system (ECC) consisting of a miniature oxygenator and heat exchanger, primed with 6 mL of asanguinous solution, was connected to a closed-chest rat with cannulae in the right atrium for venous drainage (ID = 1.7 mm) and in the ascending aorta for arterial return (ID = 1.0 mm). The rat was surface- and core-cooled until rectal temperature reached 18 degrees C, when ECC was stopped and cardioplegic solution delivered. After 5, 10, 20, 40 (each n = 5), and 80 minutes (n = 15) of HCA, the rat was reperfused, weaned from ECC, and followed with behavioral scoring, passive avoidance tasks, and cardiopulmonary exercise testing until euthanized for morphological study. Every rat resumed weight gain in the first week after HCA and regained preoperative exercise capacity by the fourth week. Only rats undergoing 80 minutes of HCA showed behavioral abnormalities such as stereotypy and incomplete righting reflex, which eventually disappeared in the fourth week. Learning ability was preserved in all except for rats after 80 min of HCA, who failed to acquire new memory to avoid electric stimuli (n = 10) up to 3 months after HCA, when pyramidal cells were partly replaced by astroglia in the cerebral cortex and CA1 sector of hippocampus. Nonetheless, old memory established before HCA was preserved even after 80 minutes of HCA and allowed rats (n = 5) to avoid electric stimuli. CONCLUSIONS: Homogeneity of animals, miniature ECC system, and an established testing system allowed evaluation of rats after HCA, which disclosed learning disability (functional disorder) and pyramidal cell loss (organic defect) after 80 minutes of HCA despite recovery of somatic function, behavior, and growth.

Animals↗
PubMed1998

Histaminergic influence on vestibular stimulation-induced locus coeruleus inhibition in rats.

In previous reports we have shown that caloric stimulation (CS) of the vestibular apparatus inhibits locus coeruleus (LC)-noradrenergic neuronal activity in urethane-anaesthetized rats. The present study examined the effect of neural histamine depletion by alpha-fluoromethylhistidine (alpha-FMH) on CS-induced LC inhibition. In alpha-FMH treated rats, LC neuronal inhibition caused by CS was still observed. This finding indicates that the central histaminergic neuron system does not participate in the CS-induced LC-noradrenergic inhibition. It is suggested that the noradrenergic neuron system is involved in the development of vestibulo-autonomic response, independent of the histaminergic neuron system.

Animals↗
PubMed1998

Glucocorticoid hormones downregulate histidine decarboxylase mRNA and enzyme activity in rat lung.

Histidine decarboxylase (HDC) is the primary enzyme regulating histamine biosynthesis. Histamine contributes to the pathogenesis of chronic inflammatory disorders such as asthma. Because glucocorticoids are effective in the treatment of asthma, we examined the effects of 6 h of exogenously administered dexamethasone (0.5-3,000 microg/kg ip), corticosterone (0.2-200 mg/kg ip), or endogenously elevated corticosterone (via exposure of rats to 10% oxygen) on HDC expression in the rat lung. HDC transcripts were decreased approximately 73% with dexamethasone treatment, 57% with corticosterone treatment, and 50% with exposure to 10% oxygen. Likewise, HDC enzyme activity was decreased 80% by treatment with dexamethasone and corticosterone and 60% by exposure to 10% oxygen. Adrenalectomy prevented the decreases in HDC mRNA and enzyme activity observed in rats exposed to 10% oxygen, suggesting that the adrenal gland is necessary for the mediation of hypoxic effects on HDC gene expression. These results demonstrate that corticosteroids initiate a process that leads to the decrease of HDC mRNA levels and enzyme activity in rat lung.

Adrenalectomy↗
PubMed1998

[Release of biogenic amines in the brain during sleep-wakefulness cycle].

Biogenic amines, including acetylcholine, act as neurotransmitters or neuromodulators in the brain of mammals. Accumulated evidences suggest the relevance of these amines to the regulatory system of sleep-wakefulness cycle. Recent development of an in vivo, microdialysis technique has revealed the existence of circadian variation in the release of these amines from various brain regions related to the regulation of sleep-wakefulness. This review focuses on the characteristics of the release of these amines determined by the microdialysis method in rats and cats during sleep-wakefulness cycle, and speculates their roles in the mechanism underlying the control of sleep and arousal state.

Animals↗
PubMed1998

Afferent reinnervation after lung transplantation in the rat.

Denervation at lung transplantation results in loss of cough reflex and attenuated local defense mechanisms, accounting for increased incidence and severity of infection after lung transplantation. We studied the presence or absence of spontaneous afferent reinnervation in rats at various intervals after orthotopic left pulmonary isografting (n = 52). Normal rats (n = 21) and rats undergoing left hilar stripping (n = 14) served as control subjects. Afferent reinnervation was tested physiologically by reflex bradycardia in response to intravenous infusion of capsaicin (30 microg/kg), an extract of paprika stimulating pulmonary C-fibers. Injection of capsaicin was repeated before and after right pulmonary artery occlusion to divert all pulmonary blood flow to the left lung or isograft. Whereas rats early after surgical denervation lost the reflex after right pulmonary artery occlusion, rats examined 8 months or longer after surgery showed potent reflex bradycardia in response to capsaicin, as did the control rats. Immunohistochemical staining for sensory neuron-specific substances, such as calcitonin gene-related peptide and substance P, were identified only in the right native lung and left pulmonary isografts 2 months or longer after transplantation. Fluorogold was found only in the ipsilateral nodose ganglion after left lung intrapleural injection of the neuron-specific tracer in rats 8 months or longer after denervation. These experiments provide physiological, morphologic, and neurologic evidence suggesting that afferent lung innervation, abolished early after transplantation, is spontaneously reestablished and functioning in the ipsilateral vagus nerve by 8 months after pulmonary isografting in the rat.

Animals↗
PubMed1997

Histamine release from the hypothalamus induced by gravity change in rats and space motion sickness.

Freely moving rats were exposed to 2 g hypergravity in an animal centrifuge device to produce motion sickness. Histamine release from the anterior hypothalamus of the rats was measured in vivo with a microdialysis technique. After a 2-h load of 2 g hypergravity, rats ate kaolin. Because pica, eating a nonnutritive substance such as kaolin, is a behavioral index of motion sickness in rats, this finding indicates that the rats suffered from motion sickness. During 2 g hypergravity for 2-h, histamine release from the hypothalamus was transiently increased. In contrast, neither the transient increase of histamine release nor the kaolin consumption were induced by 2 g hypergravity in bilaterally labyrinthectomized rats. Pretreatment with alpha-fluoromethylhistidine, an inhibitor of histamine-synthesizing enzyme, decreased both the basal and hypergravity-induced releases of histamine from the hypothalamus and suppressed the kaolin consumption induced by hypergravity. Taken together, these findings suggest that the vestibular information of changes in gravity activate the histaminergic neuron system, resulting in the development of motion sickness. More prolonged stimulation, a 4-h load of 2 g hypergravity, induced significant increase of kaolin consumption on postdays 1-3, though rats ate kaolin on postdays 1-2 after 2 g hypergravity for 2 h. During 2 g hypergravity for 4 h, the initial transient increase of histamine release was followed by the gradual increase of histamine release after the end of centrifugation. It is suggested that rats adapted to the hypergravity environment after centrifugation for 4 h, but not 2 h, so that the change in gravity from 2 g to 1 g became a provocative stimulation. We, therefore, concluded that motion sickness in rats induced by a negative change in gravity can be used as a simulation of space motion sickness, which is induced by exposure to microgravity. Histaminergic activation in the development of motion sickness induced by negative change in gravity might be an underlying mechanism of space motion sickness.

Animals↗
PubMed1997

The involvement of pertussis toxin-sensitive G proteins in the post receptor mechanism of central I1-imidazoline receptors.

1. To elucidate the possible involvement of pertussis toxin (PTX)-sensitive G proteins in the post receptor mechanism of alpha 2-adrenoceptors and imidazoline receptors, we examined the effect of pretreatment of the central nervous system with PTX on the antidysrhythmic effect of dexmedetomidine, a selective alpha 2-adrenoceptor agonist, and rilmenidine, a selective I1-imidazoline receptor agonist on halothane-adrenaline dysrhythmias in rats. 2. Dexmedetomidine (0, 1.0, 2.0, 5.0 micrograms kg-1 min-1.i.v.) and rilmenidine (0, 1.0, 3.0, 10, 20 micrograms kg-1, i.v.) prevented the genesis of halothane-adrenaline dysrhythmias in a dose-dependent fashion. Both idazoxan (10, 20 micrograms kg-1, intracerebroventricularly (i.c.v.)), an alpha 2-adrenoceptor antagonist with high affinity for imidazoline receptors, and rauwolscine, (40 micrograms kg-1, i.c.v.), an alpha 2-adrenoceptor antagonist with low affinity for imidazoline receptors inhibited the action of dexmedetomidine (5.0 micrograms kg-1, min-1, i.v.), but the inhibitory potency of idazoxan was much greater than that of rauwolscine. While the pretreatment with PTX (0.1, 0.5, 1.0 micrograms kg-1, i.c.v.) did not change the dysrhythmogenecity of adrenaline, this treatment completely blocked the antidysrhythmic property of rilmenidine (20 micrograms kg-1, i.v.) as well as dexmedetomidine (5.0 micrograms kg-1 min-1, i.v.). 3. It is suggested that central I1-imidazoline receptors as well as alpha 2-adrenoceptors may be functionally coupled to PTX-sensitive G proteins.

Adrenergic alpha-2 Receptor Agonists↗
PubMed1997

Interactions between neuronal histamine and halothane anesthesia in rats.

Using an in vivo microdialysis method, we measured the release of histamine in the anterior hypothalamic area (AHy) of rats under several concentrations of halothane anesthesia (1, 0.5, and 0.2%). The release of histamine increased to 341 and 325% at halothane concentrations of 0.5 and 0.2%, compared with the basal level at anesthesia induced by 1% halothane. alpha-Fluoromethylhistidine (100 mg/kg i.v.), a specific and irreversible inhibitor of histidine decarboxylase, reduced the histamine release to <35% of the basal value at 1% halothane anesthesia in the AHy, and also decreased the anesthetic requirement for halothane, evaluated as the minimum alveolar concentration (MAC), by 26%. Furthermore, pyrilamine (20 mg/kg i.v.), a brain-penetrating H1 antagonist, and zolantidine (20 mg/kg i.v.), a brain-penetrating H2 antagonist, reduced the MAC for halothane by 28.5 and 16%, respectively. Although thioperamide (5 mg/kg i.v.), an antagonist of presynaptic H3 autoreceptor, induced an approximate twofold increase in the level of histamine release in conscious freely moving rats, the same dose of thioperamide had little effect on the release of histamine under 1% halothane anesthesia in the AHy. Furthermore, thioperamide did not change the anesthetic requirement (MAC) for halothane. The present findings indicate that halothane anesthesia inhibits the release of neuronal histamine and that histaminergic neuron activities change the anesthetic requirement (MAC) for halothane through H1 as well as H2 receptors.

Anesthetics, Inhalation↗
PubMed1997

Lipopolysaccharide and interleukin-1beta augmented histidine decarboxylase activity in cultured cells of the rat embryonic brain.

We investigated the effect of lipopolysaccharide (LPS) and various inflammatory cytokines on the histidine decarboxylase (HDC) activity in cultured cells of the rat embryonic brain. Histaminergic neuronal cell bodies were supposed to exist in cultured cells of the diencephalon but not in those of the cortex. The HDC activity was elevated by adding LPS and interleukin-1 beta (IL-1beta) but not by tumor necrosis factor-alpha (TNF-alpha) and IL-6 to the mixed primary cultures of diencephalon. In the adherent cell fraction of the cultured diencephalon cells, HDC activity was also enhanced by LPS and IL-1beta. In a similar manner, LPS augmented HDC activity in the mixed primary culture of cerebral cortical cells and in its adherent cell fraction. The effects of IL-1beta but not LPS in the mixed primary culture of diencephalon were canceled by a prior exposure to cytosine-beta-D-arabinofuranoside. The changes in HDC activity after exposure to LPS for 12 h were not accompanied by increased mRNA levels. In these cell cultures, mast cells were not detected by Alcian Blue staining. These results indicated the presence of the third type of HDC-bearing cell besides neurons and mast cells in the brain. The increase of HDC activity by IL-1beta might be due to cell proliferation.

Animals↗
PubMed1997

Laser Doppler skin blood flow and sympathetic nervous responses to surgical incision during halothane and isoflurane anesthesia.

The aim of the present study was to evaluate whether a sudden decrease in skin blood flow measured using a laser Doppler velocimeter reflects sympathetic nervous response to surgical skin incision during halothane (n = 17) and isoflurane (n = 16) anesthesia in 33 ASA physical status I or II patients scheduled for laparotomy. Plasma norepinephrine concentrations in the responding patients who showed a sudden decrease in the skin blood flow after surgical incision increased significantly and continued to increase 1-10 min after skin incision under halothane and isoflurane anesthesia. Although plasma norepinephrine concentrations in the nonresponders did not increase after surgical incision with halothane, the concentrations increased significantly at 1 min, but not at 3 and 10 min, after skin incision with isoflurane. The results indicate that the sudden decrease in laser Doppler flow reflects the sympathetic response to surgical incision. However, these also suggest that the factors that control the skin blood flow may not be simply sympathetic but may reflect other modulators as well. Plasma epinephrine concentration increased during skin incision, but the concentrations did not differ between the patients with and without a sudden decrease in skin blood flow. Increases in systolic blood pressure and rate-pressure product on skin incision were also significantly more in patients with skin blood flow response compared with those without the response. The magnitude of changes in plasma norepinephrine concentration and hemodynamic variables with skin incision was greater with isoflurane than with halothane at the same minimum alveolar anesthetic concentration level.

Adult↗
PubMed1997

The effect of methamphetamine on histamine release in the rat hypothalamus.

In the present study, the effect of methamphetamine (MAP) on histamine (HA) release measured by in vivo brain microdialysis in the rat hypothalamus was investigated. Administration of MAP (3 mg/kg) significantly increase HA release from 40 to 160 min after the injection. This finding suggests that a moderate dose of MAP activates the hypothalamic HA neuron system, which may be related to effects of MAP on intrinsic biological rhythms.

Animals↗
PubMed1997

The effect of haloperidol on the histaminergic neuron system in the rat brain.

In this study, the effect of haloperidol on histamine (HA) levels, histidine decarboxylase (HDC) activities and the bindings of [3H]-(R)-alpha-methylhistamine ([3H]-(R)-alpha-MeHA) to histamine H3 receptors were investigated in the rat brain. Administration of 10 mg/kg of haloperidol decreased HA levels in the rat striatum and diencephalon, but increased HDC activities in rat striatum and diencephalon, although that of 5 mg/kg did not change them. Meanwhile, haloperidol inhibited the bindings of [3H]-(R)-alpha-MeHA to H3 receptor sites in the rat striatal membrane with a Ki value of 10.5 +/- 0.45 microM. These findings suggest that only a high dose of haloperidol increases HA synthesis and release as a histamine H3 receptor antagonist in the rat brain.

Animals↗
PubMed1997

Thioperamide, a histamine H3 receptor antagonist, increases GABA release from the rat hypothalamus.

Using a microdialysis method and a new high performance liquid chromatography (HPLC)-fluorometric method for the detection of gamma-aminobutyric acid (GABA), we investigated the effect of thioperamide, an H3 receptor antagonist, on the GABA content in the dialysate from the anterior hypothalamic area of rats anesthetized with urethane. The addition of thioperamide to the perfusion fluid increased the release of GABA and histamine. Depleting neuronal histamine with alpha-fluoromethylhistidine, a specific inhibitor of histidine decarboxylase, and the administration of immepip, an H3 agonist, had no effect on basal- and thioperamide-induced GABA release. In addition, an infusion of clobenpropit, the most specific H3 receptor antagonist available, did not alter the basal release of GABA. On the other hand, histamine release was decreased by immepip and increased by thioperamide and clobenpropit. Removing Ca2+ from the perfusion fluid did not alter the effect of thioperamide on the GABA release, whereas that on histamine release was abrogated. These results suggest that the effect of thioperamide on GABA release is not mediated by histamine H3 receptors and that thioperamide acts on the transporter to cause an efflux of GABA from neurons and/or glia. Thioperamide is a popular H3 receptor antagonist which has been used applied to many studies. However, results using this compound should be interpreted in consideration of its effects on GABA release.

Animals↗
PubMed1996

Brain penetration of the histamine H3 receptor antagonists thioperamide and clobenpropit in rat and mouse, determined with ex vivo [125I]iodophenpropit binding.

We investigated the brain penetration of the histamine H3 receptor antagonists thioperamide and clobenpropit using ex vivo [125I]iodophenpropit binding. Homogenates of the rat cortex, striatum and mouse whole brain were prepared 1 h after subcutaneous injection of the H3 antagonists and incubated with [125I]iodophenpropit, a radiolabeled H3 receptor antagonist, to determine the H3 receptor occupancy. Specific [125I]iodophenpropit binding to the rat cortex and striatum was inhibited by thioperamide with IC30 values of 1.0 and 1.5 mg/kg, respectively. Clobenpropit also inhibited [125I]iodophenpropit binding, but was less potent (IC30: 18 and 19 mg/kg in the rat cortex and striatum, respectively) than thioperamide. Similar results were obtained in experiments with mouse whole brain (3.5 and 13 mg/kg for thioperamide and clobenpropit), indicating that there is no important species differences in the brain penetration of these drugs between rats and mice. These findings suggest that after peripheral injection both in rat and mouse thioperamide penetrates the blood-brain barrier more efficiently compared to clobenpropit.

Animals↗
PubMed1996

Endogenous GABA modulates histamine release from the anterior hypothalamus of the rat.

Using a microdialysis method, we investigated the effects of the nipecotic acid-induced increase in content of endogenous GABA on in vivo release of histamine from the anterior hypothalamus (AHy) of urethane-anesthetized rats. Nipecotic acid (0.5 mM), an inhibitor of GABA uptake, decreased histamine release to approximately 60% of the basal level. This effect was partially antagonized by picrotoxin (0.1 mM), an antagonist of GABAA receptors, or phaclofen (0.1 mM), an antagonist of GABAB receptors. These results suggest that histamine release is modulated by endogenous GABA through both GABAA and GABAB receptors. When the tuberomammillary nucleus, where the cell bodies of the histaminergic neurons are localized, was stimulated electrically, the evoked release of histamine from the nerve terminals in the AHy was significantly enhanced by phaclofen, suggesting that GABAB receptors may be located on the histaminergic nerve terminals and modulate histamine release presynaptically. On the other hand, picrotoxin caused an increase in histamine release to approximately 170% of the basal level, and this increase was diminished by coinfusion with D(-)-2-amino-5-phosphonopentanoic acid (0.1 mM), an antagonist of NMDA receptors. Previously, we demonstrated tonic control of histamine release by glutamate mediated through NMDA receptors located on the histaminergic terminals in the AHy. These results suggest the possible localization of GABAA receptors on glutamatergic nerve terminals and that the receptors may regulate the basal release of histamine indirectly.

2-Amino-5-phosphonovalerate↗
PubMed1996

Antiarrhythmic action of rilmenidine on adrenaline-induced arrhythmia via central imidazoline receptors in halothane-anaesthetized dogs.

1. To elucidate the role of central imidazoline receptors in the genesis of adrenaline-induced arrhythmias under halothane anaesthesia, we investigated the effects of rilmenidine, a selective agonist at imidazoline receptors, on this type of arrhythmia in dogs. Rilmenidine (1, 3, 10 micrograms kg-1, i.v.) did not affect basal haemodynamic parameters (heart rate and blood pressure), but dose-dependently inhibited adrenaline-induced arrhythmias under halothane anaesthesia. 2. Although, rilmenidine has a weak affinity for alpha(2)-adrenoceptors, pretreatment with idazoxan (10 micrograms kg-1, intracisternally i.c.), an imidazoline receptor antagonist which has also alpha(2)-adrenoceptor blocking potency, blocked the antiarrhythmic effect of rilmenidine (10 micrograms kg-1, i.v.). In contrast, pretreatment with rauwolscine (20 micrograms kg-1, i.c.), a classical alpha(2)-adrenoceptor antagonist with little affinity for imidazoline receptors, did not affect the effect of rilmenidine (10 micrograms kg-1, i.v.). Furthermore, bilateral vagotomy completely blocked the antiarrhythmic action of rilmenidine (10 micrograms kg-1, i.v.). 3. It is suggested that the antiarrhythmic action of rilmenidine is due to the activation of central imidazoline receptors and that vagal tone is critical for this action of rilmenidine.

Adrenergic alpha-Agonists↗