Biomedical subjects

S Ueki

Publications and source records attributed to S Ueki.

At least 19 recordsLinked to original sources

PubMed1992

Ischemia-induced impairment of 2-deoxyglucose uptake and CA1 field potentials in rat hippocampal slices: protection by 5-HT1A receptor agonists and 5-HT2 receptor antagonists.

Various in vitro models have been developed to study ischemia and/or hypoxia. In the present experiment, we examined whether hypoxia/hypoglycemia (ischemia) in rat hippocampal slices reduced the 2-deoxyglucose (2-DG) uptake and CA1 field potentials evoked by stimulation of Schaffer collaterals. Autoradiograms revealed that ischemia for 15 or 20 min reduced 2-DG uptake in the stratum radiatum of the CA1 and the dentate gyrus. Similarly, the CA1 field potentials of slices exposed to ischemia for 15 and 20 min decreased by about 70 and 90% after a 6-h washout. In the second experiment, we evaluated the neuroprotective effect of the 5-HT1A receptor agonists 8-OH-DPAT and buspirone, and the 5-HT2 receptor antagonists cyproheptadine, mianserin and ketanserin on deficits of 2-DG uptake and Schaffer-CA1 field potentials induced by ischemia. The 5-HT1A receptor agonists and 5-HT2 receptor antagonists exhibited significant neuroprotective actions against ischemia-induced deficits. Therefore, impairments of 2-DG uptake and CA1 field potentials induced by ischemia may be good markers of ischemia-induced functional deficits. The attenuating action of 5-HT1A receptor agonists and 5-HT2 receptor antagonists were assessed using this model of ischemia.

Animals↗

PubMed1992

Pituitary adenylate cyclase activating polypeptide stimulates gallbladder motility in conscious dogs.

We investigated whether pituitary adenylate cyclase activating polypeptide (PA-CAP27 and PACAP38) had any effect on gallbladder motility in conscious dogs, in which force transducers were chronically implanted in the gastric antrum, duodenum and gallbladder. PACAP27 and PACAP38 were administered intravenously during the digestive and interdigestive states at doses of 30, 100 and 300 pmol/kg. By way of comparison, cholecystokinin octapeptide (CCK-OP) was administrated at doses of 3, 9 and 27 pmol/kg. As a result, each peptide evoked transient and tonic contractions both in the digestive and interdigestive states, and the effect on the motor index was dose dependent. PACAP27 and PACAP38 were 0.11 +/- 0.03 and 0.04 +/- 0.01 as potent as CCK-OP in the digestive state, and 0.18 +/- 0.04 and 0.02 +/- 0.01 in the interdigestive state, respectively, on a molar basis. Although PACAP27 and PACAP38 belong to the vasoactive intestinal polypeptide (VIP) family, intravenous administration of 300 pmol/kg of VIP had no effect on interdigestive gallbladder motility, but on the other hand inhibited gallbladder motility in the digestive state. The contractile effects of PACAP27 and PACAP38 were almost completely abolished by pretreatment with atropine or hexamethonium, but not with L364718. An in vitro study using canine gallbladder strips showed that PACAP27 and PACAP38 had no effect on spontaneous gallbladder motor activity evoked by electric field stimulation, CCK-OP or acetylcholine. It was concluded that PACAP27 and PACAP38 stimulate gallbladder motility in conscious dogs through a preganglionic cholinergic mechanism.

Animals↗

PubMed1992

Assessment of the role of adrenoceptor function in ischemia-induced impairment of 2-deoxyglucose uptake and CA1 field potential in rat hippocampal slices.

The release of catecholamines, dopamine and noradrenaline has been suggested to play a role in mediating ischemic damage in susceptible brain regions, the hippocampus and striatum. We now provide evidence that suggests a role for adrenoceptors in the deficit of 2-deoxyglucose uptake and CA1 field potential induced in hippocampal slices by hypoxia/hypoglycemia (ischemia). Treatment with alpha 1- or beta-adrenoceptor agonists or cAMP potentiated an ischemia-induced decline of both 2-deoxyglucose uptake and CA1 field potential in hippocampal slices, whereas alpha 1- or beta-adrenoceptor antagonists, or alpha 2-adrenoceptor agonists produced a remarkable neuroprotective action against these deficits. The results indicate that stimulation of adrenoceptors may play a detrimental role in the development of ischemic damage, and suggest a neuroprotective action for adrenoceptor antagonists, which may lessen the functional deficits induced by ischemia.

Action Potentials↗

PubMed1992

Endogenous CCK is not involved in the regulation of interdigestive gastrointestinal and gallbladder motility in conscious dogs.

In this study, we assessed whether endogenous CCK is involved in the regulation of interdigestive gastrointestinal and gallbladder motility in conscious dogs with force transducers chronically implanted in the gastric antrum, duodenum, jejunum and gallbladder. L364718 at a dose of 1.0 mg/kg was used as a specific and potent CCK receptor blocker, and its effect on spontaneous interdigestive motility and plasma motilin release were examined. Additionally, the contractile activity of exogenous synthetic canine motilin (20-100 ng/kg) with or without pretreatment with L364718 at a dose of 1.0 mg/kg was assessed. Whether the blocking effect of L364718 on CCK receptors was sufficient or not was verified by giving CCK-OP at a bolus dose of 10 ng/kg. As a result, cyclic changes in interdigestive motor activity and the plasma motilin concentration were not affected by pretreatment with L364718. L364718 also did not affect motilin-induced interdigestive contractile activity in the gastrointestinal tract and gallbladder. On the other hand, the effect of CCK-OP was completely abolished by pretreatment with L364718. It is concluded that endogenous CCK is not involved in the regulation of spontaneous and motilin-induced interdigestive contractions in the canine gastrointestinal tract and gallbladder.

Animals↗

PubMed1992

Effects of inhibitory and excitatory drugs on the metabolic rhythm of the hamster suprachiasmatic nucleus in vitro.

In order to elucidate the role of excitatory and inhibitory transmitters within the suprachiasmatic nucleus (SCN) in the circadian change of 2-deoxyglucose (2-DG) uptake in this nucleus, the effects of 8-hydroxy-2-(di-n-propylamino) tetralin hydrobromide (8-OH-DPAT), muscimol, flurazepam, pentobarbital and glutamate on uptake of 2-DG by hamster SCN were examined in hypothalamic slice preparations. 2-DG uptake in the SCN was high during the subjective day and low during the subjective night. The high uptake of 2-DG in the SCN during the daytime was inhibited by the superfusion of 8-OH-DPAT, muscimol, flurazepam and pentobarbital in a dose-dependent manner, but the low uptake of 2-DG during the night was unaffected. The low uptake during the night was significantly increased by treatment with glutamate, whereas 2-DG uptake during the day was unaffected. In contrast to the above results, 20 mM KCl and 1 microM tetrodotoxin increased and decreased 2-DG uptake during both the day and night, respectively. The present results strongly suggest that agonists of 5-HT1A receptors and GABAA-benzodiazepine-barbiturate complex receptors regulate the function of the SCN through their inhibitory action on 2-DG uptake during the day, and that glutamate also regulates SCN function through it stimulatory action on 2-DG uptake during the night.

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

PubMed1992

Protection by N-methyl-D-aspartate receptor antagonists against impairment of working memory in rats following transient cerebral ischemia.

A 5-min period of cerebral ischemia increased the number of errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points) assessed by the working memory procedure applied in a three-panel runway task. The selective and competitive N-methyl-D-aspartate (NMDA) receptor antagonist CGS 19755 (3.2 and 10 mg/kg), administered i.p. immediately after blood flow reperfusion, significantly reduced the increase in errors expected to occur 24 h after 5 min of ischemia. CGS 19755 10 mg/kg had no effect on the increase in errors when injected 6 h after ischemia. The i.p. administration of the non-competitive NMDA antagonists dextrorphan 10 and 32 mg/kg and MK-801 1.0 mg/kg immediately after reperfusion decreased the increase of errors in the ischemic rats. The protective effects of NMDA antagonists suggest that the mechanism mediated by NMDA receptors during the early reperfusion phase plays a pivotal role in the postischemic impairment of working memory.

Animals↗

PubMed1992

Effects of 5-HT1A receptor agonists on the circadian rhythm of wheel-running activity in hamsters.

The effects of 5-HT1A receptor agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), buspirone and ipsapirone on wheel-running activity in hamsters were investigated in comparison with those of GABAA receptor agonist muscimol and benzodiazepine triazolam. Intraperitoneal administration of 8-OH-DPAT, buspirone, ipsapirone, muscimol and triazolam at circadian time (CT) 8 (CT 12; onset of activity) induced a significant phase advance of wheel-running activity under constant light conditions. However, administration of these drugs at other CT points did not induce phase changes. The administration of trifluoromethylphenylpiperazine (TFMPP), a 5-HT1B receptor agonist, at CT8 produced a small phase advance. The phase advance induced by 8-OH-DPAT was blocked by pretreatment with (-)-pindolol, a 5-HT1A receptor antagonist. In addition, 8-OH-DPAT, buspirone and SM3997 accelerated the rate of re-entrainment to an 8-h phase advance in the light-dark cycle. These observations suggest that 5-HT1A receptors in the brain participate in the regulation of the circadian rhythm of wheel-running activity in hamsters.

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

PubMed1992

Analgesic and discriminative stimulus properties of U-62,066E, the selective kappa-opioid receptor agonist, in the rat.

The analgesic and discriminative stimulus properties of U-62,066E, a selective kappa-opioid receptor agonist, were investigated in the rat and compared with those of morphine. In the hot-plate test, U-62,066E produced a potent analgesic effect almost comparable to that of morphine. U-62,066E-induced analgesia was far less sensitive to antagonism by naloxone than was morphine-induced analgesia, but was potently reversed by MR-2266, a kappa-receptor antagonist. Although tolerance occurred to both U-62,066E and morphine analgesia, there was no cross-tolerance between these drugs. U-62,066E did show cross-tolerance to U-50,488H, another selective kappa-receptor agonist. Rats were trained to discriminate either 1.0 mg/kg U-62,066E or 3.2 mg/kg morphine from saline in a two-level food-reinforced procedure. The stimulus effect of U-62,066E was substituted for by U-50,488H and E-2078 a stable dynorphin derivative, but not by morphine. None of the kappa-agonists substituted for the morphine stimulus. Although U-62,066E stimulus by itself was not antagonized by MR-2266 or naloxone up to as high a dose as 10 mg/kg, the U-62,066E-like stimulus effect of U-50,488H was markedly blocked by MR-2266. The dopamine antagonists haloperidol and sulpiride substituted for the U-62,066E stimulus cue that was, however, not attenuated by the dopamine agonist lisuride. Lisuride reversed the U-62,066E-like stimulus induced by U-50,488H.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics↗

PubMed1992

[Effect of Z-103 on wound healing by dermal incision in guinea pigs].

We investigated the effects of Z-103, ZnSO4, L-carnosine and solcoseryl on wound healing by dermal incision in guinea pigs. The tensile strength, hydroxyproline contents and the value of angiogenesis (carmine contents) at the wounded site of dorsal skin were used as indices of wound healing. Z-103, given daily s.c., increased the tensile strength and hydroxyproline contents on day 4 after operation in a dose-dependent manner; in particular, the effect of 10 mg/kg of Z-103 was nearly equal to that of solcoseryl at 0.5 ml/animal. Moreover, Z-103 10 mg/kg increased the value of angiogenesis on day 3 after the operation. On the other hand, ZnSO4 and L-carnosine, components of Z-103, also similarly increased the tensile strength and hydroxyproline contents. These results suggest that Z-103 possessed an accelerative action on wound healing, and these effects may be due to the activity of its components, ZnSO4 and L-carnosine.

Animals↗

PubMed1992

Working and reference memory in rats in the three-panel runway task following dorsal hippocampal lesions.

Using a three-panel runway task, the influence of dorsal hippocampal lesions on working and reference memory in rats was investigated. Despite 20 postoperative training sessions, rats with hippocampal lesions were unable to perform the working memory task. In the acquisition process of the reference memory task, however, there was no significant difference between hippocampal- and sham-lesioned rats. On the other hand, rats trained preoperatively with a working memory procedure, and then subjected to hippocampal lesions, showed more errors (pushes made on the two incorrect panels of the three panel-gates located at four choice points) than did sham-lesioned rats. The increase in working errors induced by hippocampal lesions was not reduced during 10 subsequent re-training sessions. Hippocampal lesions had no effect on retention of the reference memory performance. The increase in working errors in hippocampal-lesioned rats was significantly reduced by treatment with the cholinesterase inhibitor physostigmine at 0.1 mg/kg and the cholinergic activating drug minaprine at 10 mg/kg. These findings suggest that lesions of the dorsal hippocampus selectively impair the ability to carry out the working memory task whether rats are trained preoperatively or postoperatively, and that the working memory loss in hippocampal-lesioned rats is mediated by lowering of the cholinergic function.

Animals↗

PubMed1992

Neuroprotective effect of WEB 1881 FU (nebracetam) on an ischemia-induced deficit of glucose uptake in rat hippocampal and cerebral cortical slices and CA1 field potential in hippocampal slices.

Effect of WEB 1881 FU (nebracetam) on hypoxia and ischemia-induced impairment of 2-deoxyglucose (2DG) uptake and CA1 field potentials induced by hypoxia and hypoxia/hypoglycemia (ischemia) in rat brain slices was evaluated and compared to the findings obtained with pentobarbital and idebenone. Hippocampal and cortical slices were exposed to 15-20 min of ischemia, and then these slices were returned to oxygenated and glucose-containing buffer for 6 hr. Ischemia reduced both 30 mM KCl-induced 2DG uptake and CA1 field potentials elicited by the stimulation of Schaffer collaterals in the hippocampus. Pretreatment of nebracetam at 1 mM or pentobarbital at 0.1 mM attenuated a decline of 2DG uptake and CA1 field potentials under the condition of ischemia. In addition, nebracetam and pentobarbital relatively recovered the increase of 2DG uptake in the hippocampus under hypoxia for 45 min. Furthermore, these drugs also attenuated the decline of 2DG uptake induced by 10 mM glutamate for 20 min. However, treatment with idebenone did not recover the deficit of 2DG uptake and CA1 field potential. The present result suggests that nebracetam and pentobarbital exert neuroprotective actions against not only ischemia but also glutamate toxicity.

Animals↗

PubMed1992

Nootropic candidates inhibit head-twitches induced by mescaline in mice.

The effects of various nootropic candidates on mescaline-induced head-twitches were studied in mice. The number of head-twitches induced by mescaline (100 mg/kg, s.c.) was significantly reduced by idebenone (32 and 100 mg/kg, i.p.), minaprine (0.32-10 mg/kg, p.o.) and nebracetam (100 mg/kg, p.o.). Cholinesterase inhibitors such as tetrahydroaminoacridine (1 and 10 mg/kg, p.o.), NIK-247 (10 and 18 mg/kg, p.o.) and physostigmine (0.32 mg/kg, i.p.) also suppressed the head-twitch response to mescaline. These results suggest that the direct or indirect cholinergic-activating effects of these drugs may be involved in inhibiting mescaline-induced head-twitches.

Animals↗

PubMed1992

Protective effect of minaprine against the abnormal changes of 2-deoxyglucose uptake by rat hippocampal slices induced by hypoxia/hypoglycemia.

Effect of minaprine on hypoxia- or hypoxia/hypoglycemia (ischemia)-induced impairment of 2-deoxyglucose (2DG) uptake by rat hippocampal slices was evaluated. Since minaprine was found to possess both a stimulating effect on acetylcholine release and a blocking effect on 5-HT2 receptors, the improving effect of minaprine on impaired 2DG uptake was compared to the findings obtained with oxotremorine, ketanserin and pentobarbital. Hippocampal slices were exposed to 20-min ischemia, and then these slices were returned to oxygenated and glucose-containing buffer for 6 hr. Ischemia reduced 30 mM KCl-induced 2DG uptake by the hippocampus. Pretreatment with minaprine, oxotremorine, pentobarbital and ketanserin attenuated the ischemia-induced decline of 2DG uptake. In addition, minaprine, oxotremorine and pentobarbital relatively recovered the increase of 2DG uptake in the hippocampal slices under hypoxia for 45 min. The present results suggest that minaprine exerts a neuroprotective action against ischemia-induced deficit of energy metabolism in vitro.

Acetylcholine↗

PubMed1991

Effect of the kappa-receptor agonist, U-50,488H, on cerebral ischemia-induced impairment of working memory assessed in rats by a three-panel runway task.

The effect of U-50,488H, a selective kappa-receptor agonist, on memory functions in an animal model of cerebral ischemia was investigated by use of a three-panel runway task. A 5-min period of ischemia caused a significant increase in the number of errors (pushes made on the two incorrect panels of the three panel-gates at four choice points) in a working memory task but it did not impair a reference memory task. U-50,488H at 10 and 32 mg/kg, administered i.p. immediately after blood flow restoration significantly reduced the increase in errors expected to occur in a working memory task assessed 24 h after 5 min of ischemia. This protective effect of U-50,488H on amnesia in the ischemic rat was antagonized by the kappa-receptor antagonist, MR-2266. We conclude that U-50,488H prevents the impairment of working memory following transient forebrain ischemia, an event mediated by the activation of the kappa-opioid receptor.

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

PubMed1991

Pharmacological profile of a potential anxiolytic: AP159, a new benzothieno-pyridine derivative.

AP159 [N-cyclohexyl-1,2,3,4-tetrahydrobenzo(b)thieno(2,3c)pyridine]-3- carboamide,hydrochloride) showed clear anti-conflict activity in rats in the absence of effects on muscle relaxation, potentiation of anesthesia (in mice) or anticonvulsant activity (in mice). This anti-conflict effect was antagonized by treatment with Ro15-1788. By contrast with the deficits produced by diazepam, AP159 did not impair passive avoidance. The latter drug also improved scopolamine-induced amnesia in the same task. AP159 did not inhibit 3H-flunitrazepam binding, but potently inhibited 3H-8OH-DPAT binding. This compound increased serotonin and 5HIAA content of the midbrain raphe nuclei and of the amygdala centralis. AP159 has been shown to be a novel non-BZP anxiolytic agent with no side effects in laboratory animals; it could be a clinically effective anxiolytic agent.

Aggression↗

PubMed1991

Involvement of the dorsal hippocampus in mediation of the antianxiety action of tandospirone, a 5-hydroxytryptamine1A agonistic anxiolytic.

The effect of tandospirone, a 5-hydroxytryptamine (5-HT)1A agonist/anxiolytic, injected directly into dorsal hippocampus, on Vogel-type conflict behavior in rats was investigated and the findings were compared with the effects of diazepam and zopiclone. Tandospirone (30 micrograms/2 microliters and 60 micrograms/2 microliters) and diazepam (40 micrograms/2 microliters) but not zopiclone (20 micrograms/2 microliters), produced a potent anticonflict action in rats. The anticonflict action of tandospirone (30 micrograms/2 microliters), injected into the dorsal hippocampus, was significantly blocked by (-)-propranolol (5 mg/kg i.p.). The present findings provide evidence that suggests that tandospirone has an antianxiety action, presumably by stimulating 5-HT1A receptors in the dorsal hippocampus.

Animals↗

PubMed1991

Cardiovascular changes induced by chemical stimulation of the amygdala in rats.

The role of the amygdaloid complex in the central regulation of the cardiovascular system was studied in unanesthetized, unrestrained rat. The injection of carbachol into the amygdaloid complex elicited a pressor response, whereas the injection of noradrenaline and 5-hydroxytryptamine into the same area caused no significant cardiovascular changes. The greatest pressor response was obtained when carbachol was injected into the central nucleus. Bradycardia and tachycardia occurred when injection of carbachol was made into dorso-central and medio-ventral parts of the amygdaloid complex, respectively. Concomitant with cardiovascular responses, the injection of carbachol into the amygdaloid complex produced behavioral changes including immobilization, body shaking, searching and rearing. The pressor response and bradycardia were suppressed by prior local injection into the amygdaloid complex of atropine but not hexamethonium. These results suggest that the cholinergic system mediated by activation of muscarinic receptors in the amygdaloid complex may play a role in the control of cardiovascular and autonomic function.

Amygdala↗

PubMed1991

[Behavioral pharmacological and electroencephalographic effects of the 5-HT1A partial agonist ipsapirone].

The behavioral and EEG effects of the 5-HT1A partial agonist ipsapirone were investigated to determine its pharmacological characteristics as an anxiolytic drug in rats, mice and rabbits, as compared with those of buspirone and diazepam. 1) The anticonflict effect of ipsapirone was almost equipotent as that of buspirone and less potent than that of diazepam in rats. Ro15-1788 antagonized the anticonflict effect of diazepam, but did not that of ipsapirone. 2) Muricide in midbrain raphe-lesioned and olfactory bulbectomized rats was inhibited by ipsapirone. However, the inhibition of muricide by ipsapirone was attenuated by its repeated administration. 3) The muscle relaxant effects of ipsapirone and buspirone on rotarod performance were less potent than that of diazepam. Ethanol-induced muscle relaxation was markedly potentiated by diazepam, but less potently by ipsapirone and buspirone. 4) The pentetrazol-induced convulsion was dose-dependently antagonized by diazepam, while it was weakly potentiated by ipsapirone and buspirone. 5) The limbic afterdischarges induced by either hippocampal or amygdaloid stimulation in rabbits were markedly inhibited by diazepam. Conversely, ipsapirone and buspirone slightly potentiated afterdischarges. In conclusion, it is suggested that ipsapirone has anxiolytic activities similar to that of buspirone and moderate antimuricidal action. In addition, ipsapirone, like buspirone, is also characterized by its less potent muscle relaxant, alcohol-potentiating and anticonvulsant actions.

Animals↗