Biomedical subjects

N Murakami

Publications and source records attributed to N Murakami.

At least 379 records · Page 21Linked to original sources

PubMed1991

Long-term cultured neurons from rat suprachiasmatic nucleus retain the capacity for circadian oscillation of vasopressin release.

We have developed a dissociated suprachiasmatic nucleus (SCN) cell culture system in order to begin a cellular analysis of the mammalian circadian oscillator. Monolayer-cultured neurons prepared from the SCN regions of 1-day-old rats were maintained in serum-free culture medium for 3-4 weeks and then perfused. In 12 out of 40 wells, a circadian oscillation of vasopressin release persisted for at least 4-5 cycles until the end of the perfusion period with no damping of the amplitude. This finding suggests that cultured SCN neurons retain the capacity for circadian oscillation for a long time, and should provide a useful model for the analysis of a mammalian circadian system at the cellular level.

Animals↗

PubMed1991

Effects of interleukins on plasma arginine vasopressin and oxytocin levels in conscious, freely moving rats.

To elucidate whether interleukins are involved in vasopressin or oxytocin release during cytokine-related stressful conditions, we examined the effects of human interleukin-1 beta and interleukin-6 on plasma vasopressin and oxytocin levels in rats. Interleukin-1 beta administrated intravenously stimulated both the vasopressin and oxytocin secretion in dose-dependent manners. Neither hormone release was observed following interleukin-6 administration. Pretreatment with aspirin significantly attenuated the effects of interleukin-1 beta on both the vasopressin and oxytocin levels. SC-19220, a prostaglandin E2 receptor antagonist, did not affect the interleukin-1 beta-induced increase of plasma oxytocin levels, but almost completely abolished its effect on plasma vasopressin levels. These results suggest that under certain stressful conditions which accompany the stimulation of cytokine production, interleukin-1 is involved in the increase of plasma vasopressin and oxytocin levels and, moreover, different kinds of prostaglandins are suggested to participate in these interleukin-1-induced hormone release.

Animals↗

PubMed1991

Effects of novel aldose reductase inhibitors, M16209 and M16287, on streptozotocin-induced diabetic neuropathy in rats.

We investigated the effects of novel aldose reductase inhibitors, M16209 (1-(3-bromobenzo[b]furan-2-ylsulfonyl)hydantoin) and M16287 (1-(3-chlorobenzo[b]furan-2-ylsulfonyl)hydantoin), on neuropathy in streptozotocin-induced (STZ) diabetic rats. Both compounds (3-100 mg/kg per day, p.o.) dose dependently improved the decreased motor nerve conduction velocity in the sciatic nerve during a 14-day treatment period. These compounds also partially ameliorated the diabetes-induced histological changes in the sciatic nerve. A distinct increase in sorbitol content and a slight decrease in myo-inositol content was observed in the sciatic nerve of STZ diabetic rats, and the sorbitol accumulation was dose dependently suppressed by treatment with M16209 and M16287. Treatment started at an earlier period was more effective in the suppression of sorbitol accumulation. There was a significant correlation between motor nerve conduction velocity and nerve sorbitol content, whereas there was none between motor nerve conduction velocity and myo-inositol content. The present study indicates that M16209 and M16287 are potent aldose reductase inhibitors expected to be useful for the treatment of diabetic complications.

Aldehyde Reductase↗

PubMed1991

Studies on the distribution of cellular myosin with antibodies to isoform-specific synthetic peptides.

Antisera were produced against two synthetic peptides having sequences specific for cellular myosin heavy chains from human macrophages (peptide IIA) and bovine brain (peptide IIB). Immunoblots of tissue extracts were made with these antibodies, and they showed that mammalian cells have at least three distinct cellular myosin heavy chain isoforms. Two of the isoforms (MIIB1 and MIIB2) were recognized by antibodies against the peptide IIB, and the other (MIIA) by the anti-peptide IIA antibodies. Polyclonal anti-platelet myosin antibodies recognized the MIIA isoform, but did not recognize MIIB1 or MIIB2. The isoforms were expressed in a tissue-specific pattern; the MIIB1 isoform was found only in brain.

Amino Acid Sequence↗

PubMed1991

Threshold dose of interleukin-1 beta for induction of an ACTH response is higher than of a febrile response.

The present study was carried out to compare the threshold doses of interleukin-1 beta (IL-1 beta) necessary to elicit febrile and adrenocorticotrophic hormone (ACTH) responses. The results show that intravenous injection of a small dose of IL-1 beta (0.2 micrograms/kg) did not stimulate ACTH secretion but induced a significant febrile response. However, intravenous injection of a higher dose of IL-1 beta (2.0 micrograms/kg) induced significant increases in plasma ACTH accompanying the fever. These results suggest that the rise in body temperature per se is not responsible for the ACTH response and that the threshold dose of IL-1 beta to induce the ACTH response is higher than that to elicit the febrile response.

Adrenocorticotropic Hormone↗

PubMed1991

Application of simultaneous determination of 3H, 14C, and 22Na by liquid scintillation counting to the measurement of cellular ion-transport.

A liquid scintillation counting method for simultaneous determination of three radioactive nuclides (3H, 14C, and 22Na) of biological interest was studied. By comparing the beta spectra of the three nuclides, their counting energy ranges, A, B, and C, were determined. 22NA was set high enough to avoid any spillover counts from lower-energy nuclides. Region A for 3H was set to maximize the counting efficiency. A good correlation between the counting efficiency for 22Na in region C and the counting efficiency of other nuclides in all regions was obtained. Prior to 3H and 14C dpm calculations, the 22Na counts spilled down in regions A and B were subtracted from the total counts in regions A and B. A simple linear equation was then used to compute 3H and 14C dpm. Findings show that the method presented is adaptable for highly quenched samples up to quenching indices of tSIE = 100. The method is useful for studying the biological transport coupled to Na+.

Beta Particles↗

PubMed1991

Rapid reentrainment of the circadian clock itself, but not the measurable activity rhythms to a new light-dark cycle in the rat.

Experiments were performed to determine if the circadian clock reentrains more quickly to an 8-hour phase shift in light-dark (LD) cycles than does the overt rhythm of activity. To investigate the reentrainment of the clock itself to an 8-hour advance or delay in the LD cycle, the rats were released into constant darkness only two or three days after a shift in LD cycle, and the amount of the phase shift of the clock itself was estimated from where free-running rhythm started by backward extrapolation. If the circadian clock could rapidly reset itself to the new LD cycle, it was predicted that the free-running rhythm of activity would start from near the dark period of the new LD cycle rather than the preceding one. When rats were released into constant darkness three days after the LD cycle was advanced by 8 hours, the activity of the free-running rhythm started near time of dark period of the new LD cycle in all rats (n = 16). When rats (n = 24) were released into constant darkness two days after the LD cycle was advanced by 8 hours, 12 rats started the activity near time of dark period of the new LD cycle, while 9 rats started the activity near time of dark period of the preceding LD cycle. The remaining 3 rats showed the activity of the free-running rhythm near intermediate phase (transient phase). On the other hand, when the rats were not released into constant darkness after LD cycle was advanced by 8 hours, it took 6.4 days for activity rhythm to reentrain to the advanced LD cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

The effect of prostaglandin E2 on the body temperature of restrained rats.

We examined the effects of intravenous (IV) or intracerebro-ventricular (ICV) injection of prostaglandin E2 (PGE2) on the rectal temperature of restrained rats. The IV injection of PGE2 (0.5 mg/kg) caused hypothermia in rats with high initial rectal temperatures, but caused an elevation in rectal temperature in those animals whose starting temperatures were low. In contrast, the ICV injection of PGE2 induced fever, regardless of the rectal temperature at the time of injection. We also examined whether temperature changes due to the IV injection of endotoxin (lipopolysaccharide, LPS, 10 micrograms/kg) or interleukin-1 beta(IL-1 beta, 0.2 micrograms/kg) were dependent upon the rats' initial rectal temperatures. Rats with low rectal temperatures developed fevers in response to LPS, while animals with high starting temperatures showed hypothermia. In contrast, the IV injection of IL-1 beta produced fever regardless of initial rectal temperature. These data suggest that PGE2 acts centrally to cause fever and peripherally to cause hypothermia, and that following the injection of LPS, these opposing actions of PGE2 may act together to determine the thermoregulatory response.

Animals↗

PubMed1991

The effect of physical restraint on IL-1 beta- and LPS-induced fever.

The stress of physical restraint has been shown to cause an elevation in the body temperature of rats. In this study, we compared the febrile responses of restrained and unrestrained animals to the injection of interleukin-1 beta (IL-1 beta) and lipopolysaccharide (LPS). We found that, prior to injection, the body temperature of the restrained animals was about 1 degree C higher than that of the unrestrained rats. The restrained rats showed significantly smaller increases in body temperature in response to the injection of either pyrogen than did the unrestrained animals.

Animals↗

PubMed1991

Fever and acute-phase response induced in rabbits by intravenous and intracerebroventricular injection of interleukin-6.

We investigated the effect of human recombinant interleukin-6 (IL-6) on body temperature and acute-phase response, including changes in plasma levels of iron, zinc, copper, and fibrinogen and in circulating leukocyte count. The intravenous (IV) injection of IL-6 (2 micrograms/kg) produced a monophasic fever. The intracerebroventricular (ICV) injection of IL-6 produced a dose-dependent fever that developed gradually and remained elevated throughout the 5-h recording period. The IV injection of IL-6 decreased the plasma concentration of iron and zinc and increased the circulating leukocyte count. The ICV injection of IL-6 resulted in similar trace metal and leukocyte changes, and increased plasma levels of fibrinogen. These results show that IL-6 can cause fever when injected IV or ICV and induces some acute-phase responses through its action on peripheral target organs and in the central nervous system.

Animals↗

PubMed1991

Structural elucidation of the 8-methoxypsoralen oxidized product that inhibits the chemotactic activity of polymorphonuclear neutrophils toward anaphylatoxin C5a.

The chemical structure of the 8-methoxypsoralen oxidized product that inhibits the chemotactic activity of anaphylatoxin C5a was determined to be 2,3-dihydro-2,9-dimethoxy-3-hydroxy-7-oxo-7H-furo[3,2-g] [1]benzopyran. Its minimal concentration required to obtain the maximum inhibition of C5a des Arg (1 x 10(-8) M) chemotactic activity is 2.5 x 10(-8) M. Bioactivity of this substance was maintained for 2 weeks, stored in a dark room at room temperature under aerobic conditions. There is a possibility that this substance may be useful in the treatment of immune complex diseases.

Chemotaxis, Leukocyte↗

PubMed1991

Prostaglandin E2 is involved in adrenocorticotrophic hormone release during swimming exercise in rats.

1. We found that adrenocorticotrophic hormone (ACTH) release in rats induced by acute swimming exercise or by an intravenous injection of human recombinant interleukin-1 beta (IL-1 beta) was significantly attenuated after chronic exercise. 2. Since involvement of prostaglandins in the ACTH response induced by IL-1 is well known, we investigated the effect of indomethacin, an inhibitor of prostaglandin synthesis, on the ACTH response induced in rats by acute swimming exercise. Pretreatment with an intravenous injection of indomethacin significantly suppressed the ACTH response induced by exercise. The effect of indomethacin (1 and 10 mg/kg) on the ACTH response was dose-dependent. 3. The effect of chronic exercise on the exercise-induced changes in the plasma concentration of prostaglandin E2 was investigated. The plasma concentration of prostaglandin E2 significantly increased after acute exercise in both the control and the chronically exercised rats. However, the increase in the plasma level of prostaglandin E2 was significantly smaller in the chronically exercised group than in the control group. 4. Intravenous injections of prostaglandin E2 produced dose-dependent increases in the plasma concentration of ACTH in rats. 5. The present results suggest that an increase in prostaglandin E2 levels in plasma is involved in the development of the ACTH response induced by exercise.

Adrenocorticotropic Hormone↗

PubMed1991

The effect of chronic exercise on the pituitary-adrenocortical response in conscious rats.

1. This study was designed to investigate the effect of chronic exercise on exercise-induced changes in plasma concentrations of adrenocorticotrophic hormone (ACTH) and corticosterone in rats. Corticotrophin releasing factor (CRF) and ACTH were injected I.V. in order to assess the responsiveness of the pituitary and adrenal glands after chronic exercise. 2. The concentrations of ACTH and corticosterone in the plasma increased significantly after acute exercise in both the control and the exercised groups but both responses were significantly smaller in the exercised group. 3. The ACTH response to I.V. CRF was also significantly smaller in the exercised rats. However, both groups of animals showed similar increases in plasma corticosterone levels after the administration of exogenous ACTH. 4. The ACTH response to CRF attenuated by repeated administration of CRF. 5. These results suggest that attenuated ACTH and corticosterone responses to acute exercise after chronic exercise result from reduced responsiveness of the pituitary gland to CRF.

Adrenal Glands↗

PubMed1991

Possible involvement of prostaglandins in psychological stress-induced responses in rats.

1. We investigated the effect of pre-treatment with intraperitoneal (I.P.) injection of indomethacin, an inhibitor of prostaglandin synthesis, on psychological stress-induced responses including cardiovascular, thermoregulatory and hormonal responses in free-moving rats. 2. Psychological stress was induced by cage-switch stress. After the rats were placed in the novel environment, blood pressure, heart rate and body temperature significantly increased. Plasma levels of adrenocorticotrophic hormone (ACTH) and prostaglandin E2 were significantly higher 30 min after exposure to stress, in comparison to normal levels. 3. Pre-treatment with I.P. indomethacin significantly suppressed the increases in body temperature induced by cage-switch stress, but had no effect on increases in blood pressure and heart rate induced by this stress. Indomethacin also significantly suppressed the increases in the plasma levels of ACTH and prostaglandin E2 induced by cage-switch stress. 4. The present results suggest that prostaglandins are involved in the development of hyperthermia and the ACTH response induced by psychological stress.

Adrenocorticotropic Hormone↗

PubMed1991

ACTH release induced in rats by noradrenaline is mediated by prostaglandin E2.

1. We investigated the involvement of prostaglandin E2 in the development of the adrenocorticotrophic hormone (ACTH) response induced by noradrenaline (NA) in rats. 2. Intravenous (i.v.) injection of NA produced dose-dependent increases in the plasma concentration of ACTH and prostaglandin E2. However, pre-treatment with systemic administration of indomethacin, an inhibitor of prostaglandin synthesis, significantly suppressed this increase in plasma ACTH. 3. The i.v. injection of prostaglandin E2 significantly increased the plasma concentration of ACTH in a dose-dependent manner. In contrast, ACTH responses induced by the i.v. injection of prostaglandin E2 were significantly suppressed by systemic pre-treatment with anti-corticotrophin-releasing factor antibody (anti-CRF), although the plasma level of ACTH still increased in comparison to the basal level. 4. These results suggest that NA-stimulated prostaglandin release is involved in the ACTH response induced by NA. In addition, it is likely that CRF may be responsible for a portion of the ACTH response induced by i.v. injection of prostaglandin E2.

Adrenocorticotropic Hormone↗

PubMed1991

Intraperitoneal injections of prostaglandin E2 attenuate hyperthermia induced by restraint or interleukin-1 in rats.

1. The purpose of this study was to investigate the effect of the intraperitoneal (I.P.), intravenous (I.V.) or intrapreoptic area (POA) injection of prostaglandin E2 (PGE2) on the body temperature of restrained and unrestrained rats. The effect of I.P. PGE2 on the body temperature of rats during fever induced by I.P. injection of interleukin-1 beta (IL-1 beta) was also investigated. 2. Prior to injection, restrained rats had body temperatures of approximately 1 degree C higher than unrestrained rats. The I.P. injection of PGE2 (0.05 and 0.5 mg kg-1) caused body temperature to fall towards the pre-restraint levels in a dose-dependent manner. This fall in body temperature was preceded by a sharp increase in tail skin temperature that was also dependent on dose. The I.P. injection of PGE2 had no effect on the body temperature of unrestrained animals. 3. The I.V. injection of PGE2 caused very little change in the body temperature of restrained rats. However, when injected I.V. into unrestrained animals, PGE2 caused dose-dependent fevers. The injection of PGE2 (50 ng) into the POA resulted in fever in both restrained and unrestrained animals. 4. The I.P. injection of IL-1 beta (10 micrograms kg-1) caused a biphasic fever that lasted at least 420 min. The I.P. injection of PGE2 180 min after the injection of IL-1 beta caused a transient decrease in the rats' body temperature. This drop in body temperature was not associated with a decrease in metabolic rate. 5. These data support the hypothesis that during restraint stress hyperthermia and IL-1 beta fever, the I.P. injection of PGE2 acts peripherally to lower the body temperature of rats.

Animals↗

PubMed1991

ACTH response in rats during biphasic fever induced by interleukin-1.

Injection of a low concentration (0.3 micrograms/kg iv) of interleukin-1 beta (IL-1 beta) produced monophasic fever, but high concentrations (15 micrograms/kg iv) produced biphasic fever in rats. Treatment with IL-1 beta caused dose-dependent rises in the plasma concentration of adrenocorticotropic hormone (ACTH) 30 min after injection. Moreover, significant increases in plasma levels of ACTH were observed 90 and 180 min after injection of the high dose of IL-1 beta. ACTH response induced by IL-1 beta (15 micrograms/kg iv) was suppressed by pretreatment with injection of indomethacin (Indo), a potent inhibitor of prostaglandin (PG) synthesis, in a dose-dependent manner (1 and 10 mg/kg iv). Also, biphasic fever induced by the high dose of IL-1 beta was completely abolished by pretreatment with the intravenous injection of Indo. Intracerebroventricular (icv) injection of Indo (50 micrograms) did not affect febrile and ACTH responses induced by intravenous IL-1 beta, whereas those responses induced by IL-1 beta (2 ng icv) were significantly suppressed by injection of Indo (50 micrograms icv). Although it is possible that intracerebroventricular Indo does not reach the site of intravenous IL-1 beta action within the brain, these results suggest that in rats febrile and ACTH responses induced by intravenous IL-1 beta are caused by IL-1 beta-acting structures outside the blood-brain barrier. It is likely that these structures subsequently synthesize and release PGE2, which in turn induces ACTH and febrile responses in rats.

Adrenocorticotropic Hormone↗

PubMed1991

Restoration of circadian corticosterone rhythm in ventromedial hypothalamic lesioned rats.

The effects of ventromedial hypothalamic (VMH) lesions on the circadian periodicity of blood corticosterone were studied in female rats. The rats were kept on a 12-hour light/12-hour dark illumination regimen and fed ad libitum. Three, 10 and 12 weeks after the VMH lesions, the concentrations of blood corticosterone were measured every 4 h for 48 h in the same unanesthetized rats. Three weeks after the operation, the circadian rhythm in VMH-lesioned rats was disturbed and disappeared. The corticosterone levels at 03:00, 07:00, and 11:00 were significantly higher than those in sham-operated rats. 10 and 12 weeks after the operation, the circadian rhythm, however, was notable (p less than 0.05, p less than 0.05). The elevated mean corticosterone levels over 48 h at 3 weeks after the operation decreased at 10 and 12 weeks. The sham-operated rats showed a significant circadian rhythm at 3, 10 and 12 weeks after the operation (p less than 0.001 in each period) with a peak concentration at 19:00 and through at 07:00. These findings show that the corticosterone circadian rhythms which were disturbed in the dynamic phase after VMH lesions recovered in the static phase of obesity, suggesting that the ventromedial hypothalamus is not an essential biological clock of circadian corticosterone rhythm.

Animals↗