Biomedical subjects

R Oishi

Publications and source records attributed to R Oishi.

At least 109 records · Page 6Linked to original sources

PubMed1990

Regulation of histamine turnover via muscarinic and nicotinic receptors in the brain.

To clarify the regulation of central histaminergic (HAergic) activity by cholinergic receptors, the effects of drugs that stimulate the cholinergic system on brain histamine (HA) turnover were examined, in vivo, in mice and rats. The HA turnover was estimated from the accumulation of tele-methylhistamine (t-MH) during the 90-min period after administration of pargyline (65 mg/kg, i.p.). In the whole brain of mice, oxotremorine, at doses higher than 0.05 mg/kg, s.c., significantly inhibited the HA turnover, this effect being completely antagonized by atropine but not by methylatropine. A large dose of nicotine (10 mg/kg, s.c.) also significantly inhibited the HA turnover. This inhibitory effect was antagonized by mecamylamine but not by atropine or hexamethonium. A cholinesterase inhibitor, physostigmine, at doses higher than 0.1 mg/kg, s.c., significantly inhibited the HA turnover. This effect was antagonized by atropine but not at all by mecamylamine. None of these cholinergic antagonists used affected the steady-state t-MH level or HA turnover by themselves. In the rat brain, physostigmine (0.1 and 0.3 mg/kg, s.c.) also decreased the HA turnover. This inhibitory effect of physostigmine was especially marked in the striatum and cerebral cortex where muscarinic receptors are present in high density. Oxotremorine (0.2 mg/kg, s.c.) and nicotine (1 mg/kg, s.c.) also decreased the HA turnover in the rat brain. However, these effects showed no marked regional differences. These results suggest that the stimulation of central muscarinic receptors potently inhibits the HAergic activity in the brain and that strong stimulation of central nicotinic receptors can also induce a similar effect.

Animals↗

PubMed1990

Effect of microinjection of histamine into the brain on plasma levels of epinephrine and glucose in freely moving rats.

The effect of histamine administered to the brain on the plasma levels of epinephrine, norepinephrine and glucose was investigated in freely moving rats. Histamine (10 micrograms) administered intracerebroventricularly (into the lateral ventricle) induced a hyperglycemic response with preceding increases in plasma catecholamines, especially epinephrine. When histamine (5 micrograms) was injected into three different levels of the ventricular system, the magnitude and duration of the resulting increases in plasma epinephrine and glucose were in the following rank order: the third ventricle greater than aqueduct much greater than fourth ventricle. These results suggest that the sites of action of histamine are located rostrally from the midbrain. Microinjections of histamine (1 microgram) into the hypothalamic nuclei including the medial preoptic area, paraventricular nucleus, ventromedial hypothalamic nucleus, posterior hypothalamic nucleus and mammillary body had no elevating effect on the plasma levels of epinephrine and glucose. Other brain regions, such as the lateral septum, medial amygdaloid nucleus and periaqueductal grey of the midbrain, were also excluded as possible sites of histamine action. From the present results, it seems that histamine stimulates plural sites close to the ventricular system to induce hyperglycemic responses.

Animals↗

PubMed1990

In vivo measurement of noradrenaline and 3,4-dihydroxyphenylethyleneglycol in the rat hypothalamus by microdialysis: effects of various drugs affecting noradrenaline metabolism.

The extracellular concentrations of noradrenaline (NA) and 3,4-dihydroxyphenylethyleneglycol (DOPEG), one of the major metabolites of brain NA, in the hypothalamus of urethane-anesthetized rats were monitored by in vivo microdialysis followed by a sensitive and simultaneous determination of the two substances using high-performance liquid chromatography with electrochemical detection. The effects of various drugs that affect central NA metabolism were also examined. Resting levels of NA and DOPEG were constant during 1 and 6 hr after the start of perfusion, the mean values being 3.8 +/- 0.4 pg/30 min for NA and 107.5 +/- 9.1 pg/30 min for DOPEG (mean +/- S.E.M. of 7 animals). Tetrodotoxin (1 microM), when added to the perfusion medium, reduced the output of NA below the detection limit (0.5 pg) and also decreased the DOPEG output by 60%. Clonidine (0.2 mg/kg i.p.) caused a marked reduction in both the NA and DOPEG outputs, whereas yohimbine (5 mg/kg i.p.) significantly increased both the NA and DOPEG outputs. Desipramine (2 and 5 mg/kg i.p.) produced a dose-dependent increase in the NA output, although it caused a gradual decline of the DOPEG output. The atypical antidepressant mianserin (2 and 5 mg/kg i.p.), which possesses both alpha-2 antagonist and weak NA uptake inhibitory actions, produced a less marked increase in the NA output with no or only a small decrease in the DOPEG output. Therefore, it is suggested that monitoring the extracellular concentrations of both NA and DOPEG enables the discrimination between the action of drugs inhibiting the NA uptake and that of drugs enhancing the NA release, and that this method is useful to obtain detailed information about central NA metabolism in vivo.

Animals↗

PubMed1989

alpha-Fluoromethylhistidine decreases the histamine content of the rat right atrium under the influence of sympathetic activity.

alpha-Fluoromethylhistidine (alpha-FMH; 65 mg/kg, i.p.), a specific inhibitor of histidine decarboxylase, significantly decreased the histamine content of the rat right atrium in a time-dependent manner; the maximal decrease of 22.2% was observed 4 h after injection. However, alpha-FMH had no significant effect on the histamine content of the left atrium or the ventricles. The alpha-FMH-induced decrease in the right atrial histamine content was not observed in rats pretreated with 6-hydroxydopamine (25 mg/kg, i.p.). Two i.p. injections of 10 and 5 mg/kg of propranolol and the cardioselective beta 1-adrenoceptor antagonist metoprolol almost completely inhibited the alpha-FMH-induced histamine decrease. On the other hand, phentolamine (10 mg/kg, i.p.) had no influence on the histamine-decreasing action of alpha-FMH. These results suggest that in the rat right atrium there is a histamine pool where a rapid turnover of histamine is maintained by normal sympathetic activity.

Animals↗

PubMed1989

Changes in histamine metabolism in the brains of mice with streptozotocin-induced diabetes.

Histamine (HA) metabolism in the brain of mice with streptozotocin (STZ)-induced diabetes was examined. The levels of tele-methylhistamine (t-MH), a major metabolite of brain HA, significantly increased 3 and 4 weeks after STZ injection. However, the HA turnover rates in the diabetic mice, determined from the accumulation of t-MH after the administration of pargyline, were not different from the control values when the animals were allowed free access to food. When the mice were starved for 15 h 4 weeks after STZ treatment, the brain levels of L-histidine decreased significantly, whereas HA turnover increased significantly. Such changes were not observed in starved control mice. Histidine decarboxylase or HA N-methyltransferase activity did not change after starvation in either diabetic or control mice. These results show that the histaminergic (HAergic) activity in the brains of diabetic mice remains within normal range as long as the animals are allowed free access to food. However, they also indicate that a marked enhancement of HAergic activity accompanied by a decrease in the brain L-histidine level occurs in starved diabetic mice.

Animals↗

PubMed1989

Effects of the histamine H3-agonist (R)-alpha-methylhistamine and the antagonist thioperamide on histamine metabolism in the mouse and rat brain.

To study the feedback control by histamine (HA) H3-receptors on the synthesis and release of HA at nerve endings in the brain, the effects of a potent and selective H3-agonist, (R)-alpha-methylhistamine, and an H3-antagonist, thioperamide, on the pargyline-induced accumulation of tele-methylhistamine (t-MH) in the brain of mice and rats were examined in vivo. (R)-alpha-Methylhistamine dihydrochloride (6.3 mg free base/kg, i.p.) and thioperamide (2 mg/kg, i.p.), respectively, significantly decreased and increased the steady-state t-MH level in the mouse brain, whereas these compounds produced no significant changes in the HA level. When administered to mice immediately after pargyline (65 mg/kg, i.p.), (R)-alpha-methylhistamine (3.2 mg/kg, i.p.) inhibited the pargyline-induced increase in the t-MH level almost completely during the first 2 h after treatment. Thioperamide (2 mg/kg, i.p.) enhanced the pargyline-induced t-MH accumulation by approximately 70% 1 and 2 h after treatment. Lower doses of (R)-alpha-methylhistamine (1.3 mg/kg) and thioperamide (1 mg/kg) induced significant changes in the pargyline-induced t-MH accumulation in the mouse brain. In the rat, (R)-alpha-methylhistamine (3.2 mg/kg, i.p.) and thioperamide (2 mg/kg, i.p.) also affected the pargyline-induced t-MH accumulation in eight brain regions and the effects were especially marked in the cerebral cortex and amygdala. These results indicate that these compounds have potent effects on HA turnover in vivo in the brain.

Amygdala↗

PubMed1989

tele-Methylhistamine levels and histamine turnover in nuclei of the rat hypothalamus and amygdala.

An HPLC method using fluorescence detection for the determination of tele-methylhistamine (t-MH) was improved to a sensitivity level which enabled the detection of 0.05 pmol of tissue t-MH. The t-MH contents and the histamine turnover rates in various nuclei of the rat hypothalamus and amygdala were subsequently measured. The histamine turnover rates were estimated from pargyline-induced t-MH accumulation. Both the t-MH levels and the histamine turnover rates were shown to be relatively high in the nuclei dorsomedialis and premammillaris ventralis of the hypothalamus, and also in the nucleus medialis of the amygdala. The steady-state t-MH levels in various nuclei of the hypothalamus and amygdala correlated well with the histamine turnover rates in these nuclei.

Amygdala↗

PubMed1989

Effect of MCI-186 on ischemia-induced changes in monoamine metabolism in rat brain.

We examined the effects of MCI-186 (3-methyl-1-phenyl-2-pyrazolin-5-one), a novel free radical scavenger and an inhibitor of ischemia-induced brain edema, on monoamine metabolism in the brains of both normal and ischemic rats. In normal rats, 3 mg/kg i.v. MCI-186, a dose that prevents ischemic brain edema, had no significant effect on brain concentrations of dopamine, norepinephrine, 5-hydroxytryptamine, or their metabolites. After the injection of 5 microliters of 3% polyvinyl acetate into the left internal carotid artery, concentrations of 3,4-dihydroxyphenylacetic acid and homovanillic acid markedly increased, but that of norepinephrine decreased, in the left telencephalon of embolized rats compared with control rats injected with vehicle; the concentration of 5-hydroxyindoleacetic acid also increased slightly. These effects were maximal 2 hours after embolization. The turnover rate of dopamine between 6 and 8 hours after embolization was significantly higher but that of norepinephrine was slightly lower than that in vehicle-treated rats. When rats were treated with 3 mg/kg i.v. MCI-186 immediately after the injection of polyvinyl acetate, the embolization-induced changes in monoamine metabolism were less marked. Our results suggest that MCI-186 attenuates ischemia-induced changes in brain monoamine metabolism, probably due to its free radical scavenging action, although it has no marked effect in normal rats.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1989

Effect of acute treatment of mice with L-histidine on the brain levels of amino acids.

The brain histidine level in mice dose-dependently increased 1 and 2 hr after an i.p. injection of 0.5-1.5 g/kg of L-histidine. The treatment with 1.0 and 1.5 g/kg but not 0.5 g/kg of L-histidine significantly decreased the brain levels of tyrosine, phenylalanine and some other amino acids 1 hr later. A complete recovery or a rebound rise of amino acid levels was observed 2 hr after treatment. These results indicate that there is a change in the transport of amino acids into the brain after treatment with large doses of L-histidine.

Amino Acids↗

PubMed1989

Effects of nociceptive stimuli on brain histamine dynamics.

The effects of nociceptive stimuli on the metabolism of brain histamine (HA) were examined, because of a previous observation that the exposure of mice to electric foot shock increased the brain HA turnover. In mice, the exposure to tail pinch markedly increased the brain level of tele-methylhistamine (t-MH), a predominant metabolite of brain HA, while the level of HA was not changed. The HA turnover, measured either by the accumulation of t-MH after pargyline injection or by the HA depletion after the treatment with alpha-fluoromethylhistidine, a specific inhibitor of histidine decarboxylase, was enhanced by the exposure to tail pinch, like the enhancement produced by the exposure to foot shock. The exposure of rats to tail pinch increased the t-MH level in the telencephalon and the midbrain. Other types of noxious stimuli, such as placing mice on a hot plate or subjecting mice to acetic acid-induced writhing, also significantly elevated the level of t-MH but not that of HA in the mouse brain. These results suggest that nociceptive stimuli produce an increase in the brain HA turnover.

Animals↗

PubMed1989

Effects of isofloxythepin on central and peripheral histamine systems.

The effects of isofloxythepin, a dibenzo[b,f]thiepin derivative, on the central and peripheral histamine systems were compared with those of chlorpromazine and haloperidol. The three drugs examined all inhibited both the histamine-induced contraction of guinea pig ileum and the specific [3H]mepyramine binding to guinea pig brain membranes in a dose-dependent manner. The effectiveness in inhibiting these reactions was in the order of: chlorpromazine greater than isofloxythepin greater than haloperidol. The histamine-induced relaxation of rat uterus, which is mediated by H2-receptors, was not affected by isofloxythepin. The effect of isofloxythepin on the pargyline-induced accumulation of tele-methylhistamine in the mouse brain was indicative of a decrease in histamine turnover, whereas chlorpromazine and haloperidol were devoid of such effects. Isofloxythepin inhibited both the lethal effect of histamine injected i.v. in mice and histamine-induced edema in rat hind paws far more strongly than chlorpromazine or haloperidol did. These results show that isofloxythepin is a neuroleptic with H1-antagonist properties, which are intermediate in potency between those of chlorpromazine and haloperidol, and also it may have an inhibitory action on histamine turnover in the brain. Protection against the lethal effect of histamine and the inhibition of histamine edema by isofloxythepin may largely be due to mechanisms other than the blocking of H1-receptors.

Animals↗

PubMed1989

Histamine turnover in the rat hypothalamic nuclei estimated from alpha-fluoromethylhistidine-induced histamine decrease.

The turnover rates, rate constants and half-life values of neuronal histamine (HA) in 10 nuclei of the rat hypothalamus were estimated from the depletion of HA induced by alpha-fluoromethylhistidine (alpha-FMH: 100 mg/kg, i.p.), a specific inhibitor of histidine decarboxylase, on the presumption that alpha-FMH depletable HA pools represent neuronal ones. Marked variation in the HA turnover rates were observed among the hypothalamic nuclei, ranging from 5.7 to 19.5 pmole/mg protein/hr.

Animals↗

PubMed1988

Histamine turnover in the brain of morphine-dependent mice.

The turnover of brain histamine was examined in mice implanted subcutaneously with a morphine pellet (50 mg free base). The numbers of naloxone-precipitated jumpings and body shakes were maximum 2 and 3 days after implantation, respectively. The brain tele-methylhistamine level significantly increased (50% to 115%) during 12 h-3 days after implantation of a morphine pellet, whereas the histamine level remained unchanged. The accumulation of tele-methylhistamine by pargyline treatment was significantly enhanced when pargyline was administered 12 h after implantation, suggesting an enhancement of histamine turnover. However, a similar degree of the tele-methylhistamine accumulation was induced by pargyline during 1-5 days after implantation, as compared with the accumulation in the control mice implanted with a placebo pellet. In mice undergoing morphine withdrawal by either the removal of morphine pellet or the treatment with naloxone 3 days after implantation, the degree of the pargyline-induced tele-methylhistamine accumulation or the (S)-alpha-fluoromethylhistidine (alpha-FMH)-induced histamine decrease was similar to that observed in the placebo pellet-control mice. The numbers of naloxone-precipitated jumpings and body shakes occurring in mice 3 days after implantation were not significantly affected by any of L-histidine, alpha-FMH or metoprine. These results suggest that turnover of histamine in the brain is enhanced by acute morphine treatment and returns to the normal rate in the stage of chronic treatment and remains unchanged during the state of withdrawal.

Animals↗

PubMed1988

Enhancement of blood-brain barrier permeability to sodium fluorescein by stimulation of mu opioid receptors in mice.

The effects of opioids on the permeability of the blood-brain barrier (BBB) were examined in mice with sodium fluorescein as an indicator of the permeability. The brain was perfused with saline 30 min after injection of sodium fluorescein (40 mg/kg, i.v.) and examined by fluorometry. Morphine hydrochloride (0.3-10 mg/kg, s.c.) markedly increased the brain level of sodium fluorescein dose-dependently without influencing the plasma level, when administered 20 min before sodium fluorescein injection. Intracerebroventricularly (i.c.v.) injected morphine hydrochloride (0.5 and 1.0 microgram) increased the brain sodium fluorescein level. Buprenorphine (0.1 and 0.5 mg/kg, s.c.) was also effective. However, pentazocine, ethylketazocine, U-50488H and SKF-10047 had no significant influence. The i.c.v. administration of [D-Ala2, MePhe4, Gly(ol)5]enkephalin (0.1 microgram) and [D-Ala2, D-Leu5]enkephalin (0.5 microgram) but not of [D-Thr2, Leu5]enkephalin-Thr increased the brain level of sodium fluorescein significantly. A small dose of naloxone (i.p.) significantly inhibited the effects of morphine, buprenorphine, [D-Ala2, MePhe4, Gly(ol)5]enkephalin and [D-Ala2, D-Leu5]enkephalin. ICI-174864 coadministered i.c.v. with [D-Ala2, D-Leu5]enkephalin was ineffective in antagonizing the effect of the latter. These findings suggest that the stimulation of mu opioid receptors results in an increase in BBB permeability to sodium fluorescein.

Animals↗

PubMed1988

Enhancement by alpha-fluoromethylhistidine of the thiopental sleep-prolonging action of delta 9-tetrahydrocannabinol.

The effect of alpha-fluoromethylhistidine (alpha-FMH), a specific inhibitor of histidine decarboxylase, on the potentiation of thiopental-induced sleep by delta 9-tetrahydrocannabinol (THC), which inhibits the histamine turnover in the brain, was examined in mice and rats. The sleeping time after injection of thiopental sodium (40 mg/kg, IV) was prolonged by THC (10 mg/kg, IP, 1 h before) to approximately twice the control value. alpha-FMH (50 mg/kg, IP) administered alone had no significant influence on the thiopental sleeping time. However, alpha-FMH given 1 or 3 h before THC treatment markedly enhanced the THC potentiation of thiopental-induced sleep. Such an enhancement by alpha-FMH was not observed when alpha-FMH was administered 15 h before THC treatment. The brain histamine level decreased by 60% during the first 4 h after alpha-FMH injection and remained low until 15 h after the treatment. The thiopental sleep-potentiating action of morphine, chlorpromazine and diazepam was not affected by pretreatment with alpha-FMH. The transient enhancing effect of alpha-FMH on the THC potentiation of thiopental-induced sleep suggests that the histaminergic system is one of the activating transmitter systems in the brain.

Animals↗

PubMed1988

Comparison of the size of neuronal and non-neuronal histamine pools in the brain of different rat strains.

The size of the neuronal and non-neuronal histamine pools in the brain of three different strains of rats was measured by assuming that the alpha-fluoromethylhistidine-induced maximal decrement of histamine represents the size of the neuronal pool. Although the total histamine levels in the brain showed a considerable interstrain variation, no significant interstrain difference was observed in the neuronal histamine level. These results suggest that the size of the neuronal histamine pool in the brain is relatively stable, whereas the size of the non-neuronal histamine pool is variable.

Animals↗

PubMed1988

Galanin inhibits noradrenaline-induced accumulation of cyclic AMP in the rat cerebral cortex.

The effect of galanin on noradrenaline (NA)-induced accumulation of cyclic AMP was investigated in slices of rat cerebral cortex. NA (10(-4)M) increased cyclic AMP levels during a 20-min observation period. Galanin (3 X 10(-7)M) significantly inhibited this response at all time points examined, although it did not change the basal levels of cyclic AMP. Galanin (10(-8)-3 X 10(-6)M) inhibited the cyclic AMP response to NA (10(-4)M) in a dose-dependent manner, with an IC50 of approximately 5.6 X 10(-8)M and a maximum inhibition of 59%. These results suggest that galanin, devoid of any detectable effects by itself, modulates the cyclic AMP response to NA in the rat cerebral cortex.

Animals↗

PubMed1988

[Turnover of brain histamine and its changes by various drugs].

Histamine (HA) is synthesized from L-histidine by histidine decarboxylase (HDC), and HA released from neurons is predominantly methylated to tele-methylhistamine (t-MH), which is further metabolized by MAO. Therefore, the HA turnover rate is determined by either a exponential decrease in HA level after treatment with alpha-fluoromethylhistidine (alpha-FMH), a specific HDC inhibitor, or a linear accumulation of t-MH after pargyline treatment. Brain HA and t-MH can be simultaneously assayed using HPLC with fluorometric detection. Care should be given to avoid the contamination by extraencephalic mast-cell HA after microwave irradiation or immersion in liquid nitrogen, and to a marked circadian variation of t-MH level. The HA turnover is the highest in the hypothalamus, low in the pons-medulla oblongata and cerebellum, and nil in the spinal cord in rats, mice and guinea pigs. The half-life of neuronal HA is 8-87 min in various brain regions of these animals. Barbiturates, enflurane, benzodiazepines, GABA-mimetic drugs, ethanol and delta 9-tetrahydrocannabinol significantly decrease the HA turnover, whereas mu-opioid agonists such as morphine and [D-Ala2, MePhe4, Gly(ol)5] enkephalin enhance it. Foot-shock and phencyclidine also enhance it at least partly via mu-opioid receptors. Chlorpromazine, haloperidol, imipramine, methamphetamine or halothane have no influence on the HA turnover.

Anesthetics↗