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T Nomoto

Publications and source records attributed to T Nomoto.

At least 109 records · Page 6Linked to original sources
PubMed1991

Influence of age on N-methyl-D-aspartate antagonist binding sites in the rat brain studied by in vitro autoradiography.

The N-methyl-D-aspartate (NMDA) receptor complex has been considered to consist of an L-glutamate recognition site, a strychnine-insensitive glycine modulatory site, and a voltage-dependent cation channel. In this study, an effect of age on NMDA antagonist binding sites was investigated through quantitative in vitro autoradiography with 3H-3-((+)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP). 3H-CPP binding sites were most concentrated in the hippocampus and cerebral cortex where NMDA receptors have been demonstrated to be involved in synaptic transmission. In aged rats, 3H-CPP binding sites in the hippocampus and cerebral cortex were not significantly changed. As for other brain regions, there was an age-dependent decline of binding sites only in the caudate-putamen and nucleus accumbens. Our previous study revealed that strychnine-insensitive glycine receptors were markedly reduced in telencephalic regions in the aged rat brain. Taking these findings into consideration, it is concluded that glycine receptors but not NMDA antagonist binding sites are severely altered in telencephalic regions of aged animals. It is considered that within the NMDA receptor complex, glycine receptors may be selectively affected in the aging process.

Aging↗
PubMed1991

Effects of two 5-hydroxytryptamine agonists on head-weaving behaviour in streptozotocin-diabetic mice.

The potencies of 5-methoxy-N, N-dimethyltryptamine (central 5-hydroxytryptamine 1 receptor agonist) and 8-hydroxy-2-(di-n-propylamino) tetralin (central 5-hydroxytryptamine 1A receptor agonist) in eliciting head-weaving behaviour were studied in streptozotocin-diabetic mice and a group of control animals. Both drugs induced head-weaving behaviour in the streptozotocin-diabetic mice and control animals, but the potencies of these 5-hydroxytryptamine 1 agonists were reduced in the streptozotocin-diabetic mice. The numbers of head weaves elicited in the streptozotocin-diabetic and control animals by the two drugs were suppressed by pre-treatment with propranolol (5-hydroxytryptamine 1A receptor antagonist) and methysergide (5-hydroxytryptamine 1 and 2 receptor antagonist), but not by ketanserin (5-hydroxytryptamine 2 receptor antagonist), confirming the involvement of the 5-HT1A receptor. Pretreatment with nicotinamide before administering streptozotocin prevented streptozotocin-induced hyperglycaemia and restored the inhibition of head-weaving behaviour observed in streptozotocin-diabetic mice. Insulin injection, which partially prevented streptozotocin-induced hyperglycaemia, completely prevented reduction of the number of head weaves elicited by 5-methoxy-N, N-dimethyltryptamine in streptozotocin-diabetic mice. These results suggest that the reduced response to 5-HT1 agonists in streptozotocin-diabetic mice may be caused by the depletion of insulin.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1991

Effect of age on alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) binding sites in the rat brain studied by in vitro autoradiography.

Receptors for excitatory amino acid, L-glutamate, have been classified into three subtypes named as N-methyl-D-aspartate (NMDA), quisqualate (QA) and kainate receptors. In the present study, an effect of age on binding sites of [3H]alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (3H-AMPA), a QA agonist, was studied in the rat brain through quantitative in vitro autoradiography. 3H-AMPA binding sites were most concentrated in the hippocampus and cerebral cortex where glutamate receptors have been demonstrated to play a role in synaptic transmission. In aged rats, 3H-AMPA binding sites in the hippocampus and cerebral cortex were not significantly changed. In our previous studies, it was noticed that strychnine-insensitive glycine receptors, which functionally coupled with NMDA receptors, showed marked age-dependent decreases in telencephalic regions. It has been shown that the glutamatergic neuronal system is involved in learning and memory. Nevertheless, it is considered that AMPA binding sites are not involved in the decline of neuronal functions, especially impairment of learning and memory, accompanying with aging process.

Aging↗
PubMed1991

Cholecystokinin increases intracellular Ca2+ concentration in cultured striatal neurons.

Although it has been established that pancreatic cholecystokinin (CCK) receptors are coupled to phosphatidylinositol turnover, the events which follow activation of CCK receptors in the central nervous system have not received much attention. In this paper, changes in intracellular Ca2+ concentration ([Ca2+]1) in response to CCK peptides were measured in single cultured rat striatal neuron by fura-2 fluorometry. CCK peptides dose-dependently increased [Ca2+]i in a monophasic manner. The order of the potencies of CCK peptides to increase [Ca2+]i was as follows: caerulein greater than CCK-8 greater than desulfated CCK-8 greater than CCK-4. The effect of caerulein was completely blocked in a Ca2(+)-depleted medium. In addition, omega-conotoxin GVIA completely inhibited the effect of caerulein, while neither nifedipine nor verapamil affected it. Our results indicate that CCK receptors couple to N-type voltage-sensitive Ca2+ channels in cultured rats striatal neurons.

Animals↗
PubMed1991

Response to opioids of isolated small intestine in the house musk shrew, Suncus murinus.

1. Response to the opioids of isolated small intestine of Suncus murinus, an insectivore, was examined and compared with that of guinea-pig ileum. 2. The mechanical response to morphine and U50,488H, preferential mu- and kappa-agonist respectively, was relaxation which was antagonized by tetrodotoxin and naloxone in the Suncus small intestine. 3. Methionine5-enkephalin and D-alanine2, D-leucine5-enkephalin, both preferential delta-agonists, elicited contraction or relaxation in the Suncus small intestine, while enkephalins elicited sustained contraction in the tetrodotoxin-pretreated intestine. 4. In the guinea-pig ileum, the response to morphine and enkephalins was consistently relaxation which was antagonized by tetrodotoxin and naloxone. 5. Morphine, D-alanine2,D-leucine5-enkephalin and U50,488H inhibited electrically-evoked twitch responses of intestine in a concentration-dependent manner in both animals. 6. The relative potencies calculated from IC50 values of opioids for twitches followed the order, D-alanine2,D-leucine5-enkephalin greater than U50,488H greater than morphine in the Suncus small intestine, whereas U50,488 greater than D-alanine2,D-leucine5-enkephalin greater than morphine in the guinea-pig ileum. 7. Suncus small intestine has unique features such that D-alanine2,D-leucine5-enkephalin was most potent in inhibiting electrically-evoked twitches and that enkephalins induced contraction following tetrodotoxin pretreatment.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1991

Analgesic effect of mu- and kappa-opioid agonists in beige and CXBK mice.

The analgesic effects of mu- and kappa-opioid agonists, including morphine, FK33,824, U50,488H, tifluadom and bremazocine, have been determined in C57BL/6J-bgJ (beige) and CXBK mice which are hyporesponsive to mu-opioid receptor-mediated analgesia compared with those of control mice (C57BL/6J (C6J), C57BL/6By (C6By), BALB/cBy (BALB] using an abdominal constriction assay. The analgesic effect of subcutaneously administered morphine and FK33,824 in both beige and CXBK mice was significantly reduced compared with the controls and the analgesic effect of U50,488H and tifluadom in beige mice was significantly reduced compared with the wild strain (C6J). No reduction of analgesic effect of U50,488H and tifluadom was seen in CXBK compared with its progenitor strains, C6By and BALB, except for a reduction of the effect of tifluadom in CXBK compared with C6By. There was no strain difference in the bremazocine-induced analgesia. These results suggest that the beige mouse has a deficit in analgesia mediated by both mu- and kappa-opioid receptors, whereas the CXBK is deficient only in the mu-opioid receptor-mediated analgesia.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1991

[8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT)-induced clonic seizure in mice].

In the present study, we examined the clonic seizure immediately preceding head-weaving behaviour elicited by 8-OH-DPAT (40 mg/kg, ip) administration in mice. 8-OH-DPAT, known to be a central 5-HT1A receptor agonist, can induce a clonic seizure. Propranolol (1, 5, 10 mg/kg, ip) and methysergide (10, 20 mg/kg, ip) reduced 8-OH-DPAT (40 mg/kg, ip)-induced head-weaving behaviour and clonic seizure, while ketanserin (125, 250, 500 micrograms/kg, ip) was without effect. Trimethadione (500 mg/kg, sc) and phenobarbital (70 mg/kg, sc) completely inhibited clonic seizure and partially inhibited the head-weaving behaviour. Morphine (50 mg/kg, sc) completely inhibited both 8-OH-DPAT-induced head-weaving behaviour and clonic seizure. These effects of morphine are naloxone (20 mg/kg, sc)-reversible. These results suggest that the clonic seizure immediately preceding head-weaving behaviour elicited by 8-OH-DPAT is mediated mainly by serotonergic receptor 1A and also by additional factors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1990

Intravenously infused adenosine increases the blood flow to brown adipose tissue in rats.

The effects of intravenously infused adenosine (ADO) and its analogues, N6-R(-)-phenylisopropyladenosine (R-PIA), 5'-N-ethylcarboxamide adenosine (NECA), on the blood flow to interscapular brown adipose tissue were studied in urethane-anesthetized rats. ADO and NECA, but not R-PIA, caused a dose-dependent increase in interscapular brown adipose tissue blood flow. The relative potency of these compounds to increase this blood flow was NECA greater than ADO greater than R-PIA. Infusing R-PIA and NECA intravenously caused a fall in diastolic blood pressure and heart rate whereas an infusion of ADO up to 380 nmol/rat per min did not elicit any systemic cardiovascular effect. A 10-mg/kg dose of alkylxanthines such as caffeine, 8-phenyltheophylline (8-PT) and 8-sulfophenyltheophylline (8-SPT) inhibited the half-maximum responses of interscapular brown adipose tissue blood flow to ADO by 41, 71 and 65% respectively indicating that caffeine is less potent than 8-PT and 8-SPT. The ADO uptake inhibitor, dipyridamole, significantly potentiated the ADO effect. These results suggest that the increased interscapular brown adipose tissue blood flow caused by ADO might possibly be mediated by A2 receptors.

Adenosine↗
PubMed1990

Age-related changes of strychnine-insensitive glycine receptors in rat brain as studied by in vitro autoradiography.

Age-related changes of strychnine-insensitive glycine receptors in the rat brain were studied through quantitative in vitro autoradiography with 3H-glycine. 3H-glycine binding sites were most concentrated in the hippocampus, cerebral cortex, and olfactory tubercle, and moderate densities of binding sites were located in the striatum, nucleus accumbens, amygdala, and certain thalamic nuclei. Low densities of 3H-glycine binding sites were observed in the lateral septal nucleus, midbrain nuclei such as the superior colliculus and central gray matter, and granule cell layer of the cerebellum. In aged animals, severe decline of 3H-glycine binding sites was observed in the telencephalic regions including the hippocampus and cerebral cortex. On the other hand, decrease of binding sites in the midbrain nuclei was of lesser degree, and there were no changes in the cerebellum. These results suggest that the decrease of glycine receptors in particular brain regions has some relation with changes of neuronal functions associated with aging process in these areas. The glutamatergic neuronal system, particularly the N-methyl-D-aspartate (NMDA) subtype, has been considered to play an important role in learning and memory. Taking into consideration that strychnine-insensitive glycine receptors are contained in the NMDA receptor complex, the present study implies that the decrease of glycine receptors may be involved in impairments of learning and memory occurring in aged brains.

Aging↗
PubMed1990

Effect of adrenergic agonists on human chorionic gonadotropin release by human trophoblast cells obtained from first trimester placenta.

The cultured syncytiotrophoblast cells from human first trimester placenta were used to determine the effect of adrenergic agonists on human chorionic gonadotropin (hCG) production in vitro. Beta-adrenergic agonists isoproterenol, ritodrine and isoxsuprine increased the hCG release during the 2 h incubation period, however, alpha-agonists norepinephrine and phenylephrine and a beta 1-agonist dobutamine had no effect. The effect of isoproterenol was blocked by propranolol and butoxamine, but less efficiently by phentolamine and atenolol. These results indicate that placental hCG production can be modulated by stimulation of beta-, possibly beta 2-adrenoceptors but not by alpha-adrenoceptors.

Adrenergic Agonists↗
PubMed1990

Successful use of vancomycin hydrochloride in the treatment of lactulose resistant chronic hepatic encephalopathy.

Vancomycin hydrochloride (2 g daily) was administered to 12 patients with cirrhosis and lactulose resistant portal systemic encephalopathy in a double blind crossover trial. All 12 patients showed a remarkable clinical improvement after vancomycin treatment. The mean (SE) electroencephalographic (EEG) frequency changed from 6.3 (0.2) to 8.5 (0.2) cps (p less than 0.001) and the mean arterial ammonia concentration from 152 (4) micrograms/ml to 97 (8) micrograms/ml (p less than 0.001). Their clinical condition deteriorated when treatment was switched to lactulose, returning to the previous slower EEG frequency and high arterial ammonia concentrations. Vancomycin seems to be effective in chronic portal systemic encephalopathy in patients who are not helped by lactulose alone.

Ammonia↗
PubMed1990

Influence of age on NMDA receptor complex in rat brain studied by in vitro autoradiography.

N-methyl-D-aspartate (NMDA) receptors are known to play an important role in learning and memory and to be involved in neuron cell death accompanying cerebral ischemia, seizures, and Alzheimer's disease. The NMDA receptor complex has been considered to consist of an L-glutamate recognition site, a strychnine-insensitive glycine modulatory site, and a voltage-dependent cation channel. In the present study, effects of age on an L-glutamate recognition site and a glycine site were examined in rat brain by quantitative in vitro autoradiography with [3H]-CPP and [3H]-glycine. Both [3H]-glycine and [3H]-CPP binding sites were most abundant in the hippocampus and cerebral cortex, and they showed a similar distribution pattern throughout the brain. [3H]-glycine binding sites were severely decreased in the telencephalic regions, including the hippocampus and cerebral cortex, in aged brain. Conversely, [3H]-CPP binding sites were well preserved in these brain areas. In the mid-brain regions and cerebellum, neither [3H]-glycine nor [3H]-CPP binding sites changed in the aged brain. Our results indicate that within the NMDA receptor complex, glycine receptors are primarily affected in the aging process.

Aging↗
PubMed1990

Serum concentrations of thyroid hormones and activity of iodothyronine deiodinase in peripheral tissues of the house musk shrew, Suncus murinus.

Serum concentrations of thyroid hormones and the properties of iodothyronine deiodinase in tissues of the house musk shrew, Suncus murinus, were examined and compared with those of the rat. Serum concentrations of thyroxine (T4) and 3,3',5'-tri-iodothyronine (rT3) were higher, while the serum concentration of 3,5,3'-tri-iodothyronine (T3) was lower in the shrew than in the rat. Among liver, kidney, skeletal muscle, heart, brown adipose tissue (BAT), spleen, lung, testes and thymus homogenates of the shrew, T(4)5'-deiodinase (5'D) activity was highest in BAT, and rT3 5'D activity was highest in both the liver and BAT. Intermediate or low T3 5-deiodinase activity was noted in all tissues examined. Activity of 5'D for T4 and rT3 in liver and kidney was much lower, while that of BAT was much higher in the shrew than in the rat. Liver and kidney 5'D may be type-I and that of BAT may be type-II in the shrew, judging from its response to 6-n-propyl-2-thiouracil and iopanoic acid and substrate preference. Thus 5'D of the shrew was similar to that of the rat in type, but was different with respect to its activity in some peripheral tissues. This difference may have relevance to the low T3 state of the shrew.

Adipose Tissue, Brown↗
PubMed1989

Postnatal changes in response to adenosine and adenine nucleotides in rat duodenum.

1. The effects of adenosine and adenine nucleotides were studied in rat duodenum from postnatal day 1 to day 70. The mechanical activity of duodenal segments was recorded through an isotonic transducer connected to a polygraphic recorder. 2. In rat duodenal segments, adenosine-5'-triphosphate (ATP, 10(-4) M) and adenosine-5'-diphosphate (ADP, 10(-4) M) produced a contractile response on postnatal day 1. This response increased with age, peaking on day 7, followed by a gradual decrease and was non-existent by day 21. In contrast, a relaxant response to ATP and ADP was apparent on day 21, and continued to increase up to day 70. 3. The contraction caused by ATP was inhibited by indomethacin or the P2y-purinoceptor antagonist, reactive blue-2 but not by tetrodotoxin or hyoscine. Thus, it may be mediated by production of prostaglandin through the P2y-purinoceptor. The relaxation produced by ATP was inhibited by reactive blue-2 but not by tetrodotoxin, guanethidine or the P1-purinoceptor antagonist, 8-phenyltheophylline indicating that ATP acts on smooth muscle directly through the P2y-purinoceptor. The pD2 for the contractile response to ATP was 5.15 on day 7 and that for the relaxant response, 6.64 on day 70. 4. Adenosine (10(-4) M) and adenosine-5'-monophosphate (AMP, 10(-4) M) elicited no response before day 14. On day 14, both adenosine and AMP produced a small relaxant response which increased with age. The relaxation produced by adenosine was inhibited by 8-phenyltheophylline but not by tetrodotoxin or guanethidine, indicating that it is mediated by an action on the P1-purinoceptor of smooth muscle. 5. It is evident from these results that in neonatal rat, a contractile response to ATP and ADP occurs initially in the duodenum, followed by a relaxant response to adenosine and AMP on day 14 and to ADP and ATP on day 21. 6. The smooth muscle of rat duodenum may tentatively be concluded to contain separate purinoceptors for adenosine and AMP (Pj) and ADP and ATP (P2) and the responses to P1- and P2-agonists change during the course of development.

Adenine Nucleotides↗
PubMed1989

Effect of reserpine pretreatment on brown fat iodothyronine 5'-deiodinase of mouse.

The effect of pretreatment with reserpine (1 mg kg-1 i.p. daily for 7 days) on the regulation of iodothyronine 5'-deiodinase (5'D) in mouse brown adipose tissue (BAT) has been examined. 5'D activity of BAT homogenate was assessed by the in-vitro formation of 3,5,3'-triiodothyronine from thyroxine and 3,3'-diiodothyronine from 3,3',5'-triiodothyronine in the presence of 20 mM dithiothreitol. Reserpine treatment decreased the stimulation of BAT 5'D induced by acute cold exposure (4 degrees C, 2 h) without a significant decrease in the basal 5'D activity, whereas stimulation of BAT 5'D elicited by noradrenaline (0.4 and 0.8 mg kg-1 s.c. 2 h previously) was not augmented after reserpine treatment. Although both noradrenaline and acute cold exposure increase BAT 5'D through alpha 1-adrenoceptors, our results show that chronic reserpine treatment prevents the effect of cold, but does not induce alpha 1-adrenoceptor supersensitivity in BAT.

Adipose Tissue, Brown↗
PubMed1989

Developmental changes in the effects of carbachol and morphine on cGMP contents of plasma, heart, and lung of mice.

It is considered that carbachol increases plasma cGMP levels by acting on muscarinic receptors and morphine increases these levels by acting on opioid receptors, followed by stimulation of muscarinic receptors. We investigated the ability of carbachol and morphine to increase cGMP contents of plasma, heart, and lung and the guanylate cyclase activity of heart and lung homogenate in 1-, 2-, 3-, and 7-week-old mice. The increase in plasma cGMP levels induced by carbachol showed a peak at 2 and 3 weeks of age. The basal cGMP contents in heart and lung and their rise induced by carbachol, as well as the guanylate cyclase activity of these organs, were decreased in 7-week-old mice. The effects of morphine on the cGMP contents showed a similar developmental change, except for no effect in 1-week-old mice. These changes in the effects of carbachol and morphine may be the result of developmental changes of the muscarinic receptor--guanylate cyclase system and opioid receptors.

Aging↗
PubMed1989

Properties of 5'-deiodinase of 3,3',5'-triiodothyronine in rat skeletal muscle.

To characterize rT3 5'-deiodinase (5'D) in rat skeletal muscle, the effects of altered thyroid status and PTU on rT3 5'D were studied. rT3 5'D activity was measured by incubating homogenates of rat skeletal muscle with [125]rT3, iodine labelled in the outer ring, in the presence of 20 mmol/l DL-dithiothreitol. This activity was observed to increase significantly 24 h after a single sc injection of T3 (75 micrograms/kg). The increase following the daily administration of this drug (15 or 75 micrograms/kg) for 3 and 14 days was dependent on the dose and number of previous days of injection. A significant decrease in activity was observed 2 weeks after thyroidectomy. The addition of 0.1 mmol/l 6-n-propyl-2-thiouracil (PTU) to the incubation medium in vitro caused a marked reduction in the activity in homogenates of skeletal muscle from hypothyroid, euthyroid and hyperthyroid rats. PTU, present at 0.05% in the drinking water for 2 weeks virtually abolished it. The properties of rT3 5'D in rat skeletal muscle thus appear to be essentially the same as those of type I enzyme with respect to response toward altered thyroid status and PTU.

Animals↗