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Biomedical subjects

S Ueki

Publications and source records attributed to S Ueki.

At least 91 records · Page 5Linked to original sources
PubMed1989

[Estrogen production in epithelial tumors of the ovary--localization of estrogen-synthesizing cells].

The origin of the elevated serum estrogen in postmenopausal patients with common epithelial tumors of the ovary was investigated by means of endocrinological, histochemical, immune histochemical and autoradiographic techniques. Estrone and estradiol and their precursors were quantitatively extracted from the tumor tissue homogenate, and the results indicated that the estrogen-producing pathway was not uniform among the tumors. On the tissue section Sudan-IV staining showed positive in the stromal area in the form of fine granules or droplets. The immune peroxidase method revealed that the Sudan staining-positive substance included estrogen and its precursors. Estrogen was also detected in the epithelium, but it seemed to be present in the epithelial (tumor) cells as an estrogen-estrogen receptor complex. Cholesterol staining was focally positive in the subepithelial stromal area and incorporation of 3H-cholesterol into the stromal cells was observed by microautoradiography. These findings indicated that steroid synthesis from cholesterol to estrogen appeared in the stroma of the tumor and high serum concentrations of estrogen in the patient were the result of accelerated estrogen-synthesis in the ovarian tumor.

Autoradiography↗
PubMed1988

A selective kappa-opioid agonist, U-50,488H, blocks the development of tolerance to morphine analgesia in rats.

The development of tolerance to morphine analgesia was completely blocked by the coadministration of a selective kappa-opioid agonist, U-50,488H at doses of 3.2 or 10 mg/kg i.p. These doses of U-50,488H exerted no analgesic effect by themselves and did not affect the analgesia induced by 10 mg/kg of morphine. The analgesic effect of morphine was restored when 10 mg/kg of U-50,488H was coinjected in morphine-tolerant rats. These findings suggest that activation of the kappa-opioid system prevents the development of tolerance to morphine analgesia.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
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

Gastric motility is an important factor in the pathogenesis of indomethacin-induced gastric mucosal lesions in rats.

Effects of atropine, cimetidine, and 16,16-dimethyl prostaglandin E2 (16,16-dmPGE2) on indomethacin-induced gastric lesions were investigated in rats by correlating their effects on gastric acid and HCO3- secretion and motility. Subcutaneously administered indomethacin (25 mg/kg) produced gastric mucosal lesions within 4 hr. In parallel studies, an equivalent dose of indomethacin inhibited gastric HCO3- secretion, and stimulated gastric motor activity measured as intraluminal pressure recordings, whereas acid secretion was unaffected. The lesions induced by indomethacin were significantly prevented by three agents: cimetidine (100 mg/kg), which reduced acid secretion; atropine (1 mg/kg), which reduced acid secretion and gastric motility; and 16,16-dmPGE2 (10 micrograms/kg), which reduced acid secretion and motility and increased gastric HCO3- secretion. If acid (150 mM HCl) was infused into the stomach (1.2 ml/hr) during indomethacin treatment, only the latter two agents significantly prevented the formation of gastric lesions in response to indomethacin. Since only the effect on gastric motility was common to these two agents (atropine and 16,16-dmPGE2), the increased gastric motility may be an important pathogenetic factor in indomethacin-induced gastric lesions. The presence of acid as well as a deficiency of endogenous PGs may be prerequisite for later extension of the lesions but cannot account for the induction of mucosal lesions in rats following administration of indomethacin.

16,16-Dimethylprostaglandin E2↗
PubMed1988

Anti-serotonin action in combination with noradrenaline-stimulating action is important for inhibiting muricide in midbrain raphe-lesioned rats.

The present study was designed to examine the possible involvement of both an anti-serotonin action and a catecholamine-stimulating action in the mechanism of the inhibition of the muricide in rats with lesions of the midbrain raphe. Serotonin antagonists, such as cyproheptadine (10 mg/kg), cinanserin (10 mg/kg) and pirenperone (1 mg/kg), given alone showed little suppression of muricide in rats with raphe lesions, although the first two drugs were inhibitory at very large doses. Methamphetamine showed no inhibition of muricide at 0.32 mg/kg (i.p.), but exerted a marked inhibition of muricide when combined with the above serotonin antagonists. In addition, the dose-response curve for cyproheptadine and cinanserin was shifted markedly to the left when combined with L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) (100 mg/kg i.p.), but not with lisuride (0.32 mg/kg i.p.). Similarly, pirenperone produced a marked inhibition of muricide at doses of 0.32-1.8 mg/kg (i.p.) when combined with L-threo-DOPS, but not when combined with lisuride. These results suggest that the combination of an anti-serotonin action with noradrenergic activation is important for inhibiting muricide, at least in rats with raphe lesions. A similar mechanism also seems to be valid for the anti-muricidal effect of antidepressant drugs.

Aggression↗
PubMed1988

Stimulatory action of gamma-aminobutyric acid on catecholamine secretion from bovine adrenal chromaffin cells measured by a real-time monitoring system.

The present study was designed to evaluate the role of gamma-aminobutyric acid (GABA) in the secretory function of cultured chromaffin cells using the method of real-time monitoring. GABA evoked the secretion of catecholamines (CA) from adrenal chromaffin cells in a dose-dependent manner. Bicuculline 10(-5) M inhibited the stimulatory action of GABA. Diazepam 5 X 10(-6) and 2.5 X 10(-5) M facilitated the secretory response evoked by 7 X 10(-5) M GABA by 22% and 96%, respectively, which was antagonized by Ro 15-1788. This finding suggests that GABA-benzodiazepine receptor coupling can function in the secretion of CA from the adrenal chromaffin cells in a manner similar to that observed in the brain. GABA-evoked release of CA was reduced by 1 microM nifedipine to 16% of control, suggesting the involvement of voltage-sensitive Ca2+ channels in the mechanisms of the CA-releasing action of GABA in these cells. From these findings, the involvement of GABAergic mechanisms in the regulation of adrenal medullary function can be proposed.

Adrenal Glands↗
PubMed1988

Involvement of the medial amygdaloid nucleus in the action of imipramine in rats subjected to the forced swimming test.

A forced swimming test proposed by Porsolt is a useful method for screening antidepressants. To evaluate drug effects more objectively, vibration of the walls of a water tank caused by the escape behavior of the rat was recorded. Imipramine (IMI) increased the number of vibration and this effect was observed in the medial amygdala lesioned rat but not in the central or basolateral amygdala lesioned rat. The present result suggests that the medial amygdala is an important site of action of IMI.

Amygdala↗
PubMed1988

[Behavioral effects of quinupramine, a new tricyclic antidepressant].

The effects of a new tricyclic antidepressant quinupramine (5-(3-quinuclidinyl)-10,11-dihydro-5H-dibenz [b, f] azepine) on various animal behaviors were examined in mice and rats and compared with those of imipramine, amitriptyline and maprotiline. Quinupramine antagonized haloperidol-induced catalepsy and tetrabenazine-induced ptosis and potentiated methamphetamine- and apomorphine-induced stereotyped behavior. These effects were almost the same as or even more potent than those of imipramine and amitriptyline. Quinupramine decreased locomotor activity in mice, but potentiated methamphetamine-induced hyperactivity to a greater degree than imipramine and amitriptyline. On the other hand, quinupramine inhibited muricide in accumbens-lesioned rats, but did not prominently inhibit muricide in olfactory-bulbectomized and raphe-lesioned rats. Quinupramine decreased the duration of immobility in low doses without affecting locomotor activity, and this effect was almost the same as that of imipramine and amitriptyline and more potent than that of maprotiline. Quinupramine antagonized physostigmine lethality and oxotremorine-induced tremor, suggesting that quinupramine has a central anticholinergic action. Quinupramine, like imipramine and amitriptyline, has no effect on conditioned avoidance behavior. In conclusion, quinupramine generally has the same behavioral profile as typical tricyclic antidepressants, but it has somewhat different effects from imipramine and amitriptyline since quinupramine has a potent central anticholinergic and a weak antimuricide effect.

Animals↗
PubMed1988

A new method for studying working memory by using the three-panel runway apparatus in rats.

We designed a new method for studying working memory, by using a repeated acquisition procedure in the three-panel runway apparatus. This apparatus is composed of a start box, a goal box and four consecutive choice points; each choice point consists of three panel gates. Male Wistar rats were trained with 6 consecutive trials (one session) per day. Each trial was performed every two minutes. In this apparatus, rats could pass through only one gate (correct gate) among three panel gates in the direction of the goal box and were given 100 mg food pellets as the positive reinforcement. The sequence of correct gate position in each rat was changed everyday, but not in each session. Error responses (pushing the incorrect gate) were gradually reduced as training was repeated, and the learning was established within 16 training sessions to achieve criterion performance. Intraperitoneal scopolamine and intrahippocampal ethylcholine aziridinium ion (AF64A) produced increases in both the number of errors and the latency in a dose-dependent manner. The increase in errors induced by AF64A did not return to the control level, though the prolonged latency returned to normal. As a conclusion, this experimental procedure using the three-panel runway apparatus would be a useful method for studying working memory, and its memory deficit is involved at least in the dysfunction of the cholinergic system in the hippocampus.

Animals↗
PubMed1988

The effect of agonists at the GABA-benzodiazepine-receptor-complex on the proconflict effect induced by beta-CCM and pentetrazol in rats.

The effect of anxiolytics, benzodiazepine (BZP), diazepam (DZP), non-BZP zopiclone (ZOP) and phenobarbital (PBT), on the proconflict effect induced by methyl-beta-carboline-3-carboxylate (beta-CCM) or by pentetrazol (PTZ) was investigated. The proconflict effect of beta-CCM and PTZ was reduced by these anxiolytics and aminooxyacetic acid (AOAA). In addition, isoniazid produced proconflict activity. Therefore, it is suggested that anxiolytics facilitate the GABA-ergic function, causing the inhibition of the proconflict effect. Although both propyl-beta-carboline-3-carboxylate (beta-CCP) and Ro15-1788 did not produce proconflict activity, they reduced the proconflict effect induced by beta-CCM but not by PTZ. These data clearly show that beta-CCM exerts the proconflict effect through interaction with BZP receptor and that there are behavioral similarities between beta-CCP and Ro15-1788. In this study, we additionally observed the time latency until the rat began to drink the water. beta-CCM and PTZ prolonged this latency in a dose-dependent manner. However, AOAA could not reduce the prolonged latency induced by beta-CCM and by PTZ, and anxiolytics and beta-CCP could not reduce the prolonged latency induced by beta-CCM. The mechanism of the prolongation of latency induced by beta-CCM and PTZ seems to be different from that of the proconflict effect.

Aminooxyacetic Acid↗
PubMed1988

The effect of a selective phosphodiesterase inhibitor, rolipram, on muricide in olfactory bulbectomized rats.

In order to evaluate the potential usefulness of the drug as an antidepressant, acute and chronic effects of rolipram, a selective inhibitor of Ca2+- and calmodulin-independent cyclic AMP phosphodiesterase were investigated on muricide in olfactory bulbectomized (OB) rats. Upon single administration to OB rats, rolipram at a dosage of 1 mg/kg body weight suppressed the muricide for 2 hr after its administration. As a consequence of daily administration of rolipram, however, the incidence of muricide at 24 hr after the administration was decreased, and more than 60% of the rats did not exhibit the muricide on the 12th day. After the cessation of the administration, the incidence of the muricide returned to the initial level. The suppression of the muricide was not antagonized by several kinds of neurotransmitter blockers. Administrations of phosphodiesterase inhibitors and dibutyryl cyclic AMP as well as desipramine and clomipramine also suppressed the muricide dose-dependently. Repeated administration of desipramine also gave results similar to those of rolipram: repetition of a short suppression on the muricide was followed by the appearance of a long-lasting suppression. Differently from rolipram and desipramine, dibutyryl cyclic AMP did not cause long-lasting suppression, and even the direct effect (75% suppression) observed 30 min after its administration on the first day disappeared during its repeated administration for 14 days. From these results, rolipram was considered to show an antidepressant effect through the inhibition of Ca2+- and calmodulin-independent cyclic AMP phosphodiesterase.

Animals↗
PubMed1988

Electroencephalographic effects of the new antidepressant paroxetine in the rabbit.

The electroencephalographic (EEG) effect of (-)-trans-4-(4'-fluorophenyl)-3-(3',4'-methylene-dioxyphenoxy-met hyl)piperidine hydrochloride (paroxetine, BRL 29060A) a new antidepressant, was investigated in conscious rabbits with chronic electrode implants and was compared with those of imipramine and amitriptyline. Paroxetine induced an arousal pattern of the spontaneous EEG consisting of low voltage fast waves in the cortex and synchronization of hippocampal theta waves with decreased amplitude, while imipramine and amitriptyline elicited drowsy patterns of the spontaneous EEG. Paroxetine failed to suppress the EEG arousal responses induced not only by auditory stimulation but also by electrical stimulation of the mesencephalic reticular formation, centromedian thalamus and posterior hypothalamus, whereas imipramine and amitriptyline markedly inhibited these responses. The EEG arousal response induced by i.v. injection of physostigmine 0.2 mg/kg was slightly enhanced by paroxetine, while the response was significantly suppressed by imipramine and amitriptyline. Paroxetine, imipramine and amitriptyline showed no significant effect on the photic driving response and recruiting response. Paroxetine did not show any effects on the limbic afterdischarges elicited by either hippocampal or amygdaloid stimulation, while imipramine and amitriptyline caused an initial suppression followed by slight enhancement of these afterdischarges. These results indicate paroxetine to be an antidepressant of a new type which induces a sustained arousal pattern of the spontaneous EEG and has no central anticholinergic action.

Amitriptyline↗
PubMed1987

The effect of agonists at the GABA-benzodiazepine receptor complex on the duration of immobility of mice in the forced swimming test.

In the present study, we examined the effect of various agents which affect in a different manner the GABA-benzodiazepine receptor-chloride ionophore complex system in relation to the immobile behavior of mice in the forced swimming test. The benzodiazepines diazepam and flurazepam, the barbiturates pentobarbital and phenobarbital, zopiclone and beta-CCP (propyl-beta-carboline-3-carboxylate) enhanced the immobile behavior in a dose-dependent manner. In the doses used here, these agents produced almost no muscle relaxant action. Ro15-1788 and beta-CCM (methyl-beta-carboline-3-carboxylate) themselves had no effect on the duration of immobility. However, Ro15-1788 and beta-CCM reversed the enhancing effect produced by all 6 drugs. These results indicate that the enhancement of the duration of immobility of mice may be somehow correlated to the anxiolytic action but not to the muscle relaxant action. The effect may be mainly mediated by the benzodiazepine receptor, which forms a part of the GABA-benzodiazepine receptor-chloride ionophore complex. Furthermore it is suggested that there were behavioral similarities in the effects of beta-CCP and benzodiazepines.

Animals↗
PubMed1987

Differential mechanisms involved in the anticonflict action of benzodiazepines injected into the central amygdala and mammillary body.

The present study was designed to clarify the mechanism of action of benzodiazepines (BDZ) injected into the central amygdala (ACE) and mammillary body (MB). When gamma-aminobutyric acid (GABA) at doses of 30 and 70 micrograms, muscimol (0.01 and 0.03 microgram), valproate (200 micrograms), atropine (20 micrograms) and cyproheptadine (3 micrograms) were bilaterally injected into ACE, a significant and marked increase in the punished responses of conflict schedule was observed. These drugs injected into MB failed to increase the punished responses. In MB, only noradrenaline (NA, 20 micrograms) showed the anticonflict action. NA 20 micrograms also produced the anticonflict action in ACE. These results suggest that the mechanism of anticonflict action of BDZ is different in brain areas. The GABA-ergic, cholinergic, serotonergic and NA-ergic systems seem to be involved in the mechanism of anticonflict action of BDZ in ACE. While the NA-ergic system appears to be operative in MB.

Amygdala↗
PubMed1987

Clonidine attenuates wet-dog shaking induced by hippocampal stimulation in rats.

The effect of an alpha 2-adrenoceptor agonist, clonidine on wet-dog shaking (WDS; also, WDS = wet-dog shakes) induced by electrical stimulation of the hippocampus was investigated. Clonidine (0.01-0.32 mg/kg i.p.) inhibited the appearance of WDS in a dose-dependent manner without showing any effect on hippocampal afterdischarge. Although clonidine has been reported to inhibit the activity not only of noradrenergic but also of serotonergic neurons, a 5-hydroxytryptamine (5-HT) antagonist, cinanserin at doses up to 32 mg/kg had no significant effect on hippocampal stimulation-induced WDS. Therefore, a possible anti-5-HT action of clonidine in the inhibition of WDS can be excluded. The WDS inhibition produced by clonidine was blocked significantly by pretreatment of the rats with an alpha 2-adrenoceptor antagonist, yohimbine, but not with a narcotic antagonist, naloxone. The present results suggest that a central noradrenergic function may be involved in WDS induced by hippocampal stimulation.

Animals↗