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T Ono

Publications and source records attributed to T Ono.

At least 1,045 records · Page 58Linked to original sources
PubMed1987

Bacterial synthesis of recombinant alpha-human atrial natriuretic polypeptide.

The high-level synthesis of alpha-human atrial natriuretic polypeptide hormone in Escherichia coli has been achieved based on the idea that the yield of a small, basic and unstable polypeptide, such as the natriuretic polypeptide, would be improved by fusion with an appropriate protective polypeptide to construct a neutral fused polypeptide. We prepared an expression vector, pCLaHtrp3t, coding a neutral polypeptide containing 130 amino acid residues in which the polypeptide hormone was fused to a newly designed protective polypeptide through lysine as an enzymatically cleavable residue. The fused polypeptide was synthesized at the high level of 32% of total cellular proteins and at 4.7 X 10(6) molecules per single cell. It was recovered as cellular insoluble fraction and purified to homogeneity. For the isolation of the peptide hormone from the resultant fused polypeptide, Achromobacter protease I, a lysine-specific endopeptidase was used, because it has sufficient activity even in 8 M urea. The recombinant natriuretic polypeptide was indistinguishable from native alpha-human atrial natriuretic polypeptide as regards amino acid sequence as well as biological activity.

Amino Acid Sequence↗
PubMed1987

Disruption of seminiferous epithelial function in the rat by ovarian protein.

The granulosa cell produces an inhibitor of aromatase activity, which recently was purified to homogeneity (follicle-regulatory protein: FRP). Since extracts of testicular homogenates also contain factor(s) with biological properties similar to FRP, including inhibition of granulosa cell aromatase, we examined the effects of ovarian FRP on testicular function. Forty-five-day-old rats received daily FRP injections (100 micrograms or 300 micrograms). After 15, 30, 45, and 70 days of therapy, (n = 5 each group), trunk serum was measured for testosterone, androstenedione, estradiol, and FSH levels by established radioimmunoassays (RIA). One testis from each rat was homogenized, centrifuged, and evaluated for sperm head counts; the other testis was dissected by transillumination, and the length of seminiferous epithelial stages determined. After 15 (control: 4.8 +/- 0.2 mm; 100 micrograms: 6.0 +/- 0.3 mm; 300 micrograms: 6.6 +/- 0.3 mm) and 30 days (control: 4.6 +/- 0.2 mm; 100 micrograms: 6.3 +/- 0.2 mm; 300 micrograms: 5.9 +/- 0.2 mm) of treatment the length of the "strong" seminiferous tubule segment in FRP-treated rats was greater than in control rats (p less than 0.05). Serum levels of steroids and FSH were similar in all groups. After 30, 45, and 70 days of treatment, the sperm head counts for the 100-micrograms and 300-micrograms dosages were 26%, 29%, 30% and 20%, 34%, and 24% of control values, respectively. By 70 days of treatment, cycle Stage VII was markedly reduced or absent in FRP-treated rats, and their round spermatids contained ring chromatin; both conditions indicate degeneration. FRP (50 micrograms/ml) was added to rat Sertoli cell cultures for 4 days after which transferrin and androgen-binding protein (ABP) were measured. FRP enhanced Sertoli cell secretion of ABP (58 vs. 138 +/- 7 microliters eq/culture) and transferrin (2.1 vs. 4.7 +/- 0.6 microgram/culture). In conclusion, systemic injection of FRP alters seminiferous epithelial function by reducing maturation of mature sperm forms. Adding FRP to Sertoli cells in culture enhances secretion of transferrin and ABP; this suggests that maturation of the germinal elements may be linked to the secretory function of seminiferous tubules.

Androgen-Binding Protein↗
PubMed1987

Diurnal- and behaviour-related activity of ventromedial hypothalamic neurones in freely behaving rats.

1. Long-term (25-93 h) single-neurone activity of seventy-eight ventromedial hypothalamic (v.m.h.) neurones was analysed in freely behaving rats. 2. The activity of fifty-seven (73%) of the seventy-eight neurones tested depended on arousal and sleep, determined by electroencephalogram (e.e.g.), and varied diurnally. The activity of 39.8% (31/78) increased during e.e.g. arousal, and decreased during slow-wave sleep. Activity of 33.3% (26/78) varied inversely. 3. The activity of 21.8% (17/78) was independent of e.e.g. arousal and sleep. The activity of all except one of the seventeen increased in the dark period and varied diurnally. Activity of one increased during light stimulation. 4. The activity of the remaining 5.1% (4/78) was less than 0.5 spikes/s, and was not related to e.e.g. arousal or sleep or the diurnal cycle. 5. The effects of bilateral lesions of the suprachiasmatic nuclei (s.c.n.) were investigated on six v.m.h. neurones. All of these lost their diurnal variation; five retained their dependence on e.e.g. arousal and sleep, and one retained its independence of e.e.g. arousal and sleep. 6. There was no discernible relation between v.m.h. recording site and any of the tested characteristics of these neurones. 7. Of seventy-eight v.m.h. neurones tested, seventy-four were classified as either: (1) diurnal, sleep-arousal related, or (2) diurnal, sleep-arousal independent. Because s.c.n. lesions abolished the circadian rhythm of v.m.h. activity in every neurone tested, it was concluded that at least some v.m.h. diurnal variation is driven from the s.c.n. as a biological clock. It is clear also that responses related to e.e.g. are driven from some source other than the s.c.n.

Action Potentials↗
PubMed1987

Feeding- and chemical-related activity of ventromedial hypothalamic neurones in freely behaving rats.

1. The activity of seventy-eight single neurones in the ventromedial hypothalamus (v.m.h.) was recorded in sixty-three freely behaving rats, and the effects of feeding, intraventricular (I.C.V.) administrations of noradrenaline, glucose, NaCl and ambient temperature on neuronal activity were analysed. If I.C.V. NaCl had an effect, intraperitoneal (I.P.) NaCl, mannitol and polyethylene glycol were also tested. 2. Neurones in the v.m.h. were classified into three groups according to diurnal variations and their relations to electroencephalogram (e.e.g.) and responses to feeding: diurnal-e.e.g. related (57/78, 73.1%); diurnal-e.e.g. independent (17/78, 21.8%); non-diurnal-e.e.g. independent (4/78, 5.1%). Of fifty-seven e.e.g.-related neurones, twenty-six decreased activity during feeding episodes. Of seventeen e.e.g.-independent neurones, eight increased activity gradually during feeding and sustained the increase after the feeding episode. The response magnitude of two e.e.g.-independent neurones depended on the kind of food available. 3. Of twenty-five e.e.g.-related neurones tested, twelve responded to I.C.V. noradrenaline, but not to I.C.V. glucose or NaCl. Neurones independent of e.e.g. responded variously to I.C.V. noradrenaline, glucose and NaCl. When I.C.V. NaCl had an effect, I.P. NaCl, mannitol and polyethylene glycol had the same effect. The activity of three neurones was increased by I.C.V. glucose and decreased by I.C.V. noradrenaline, but was not changed by I.C.V. NaCl. The activity of three was increased by I.C.V. glucose and decreased by I.C.V. NaCl and by I.C.V. noradrenaline. The activity of five was increased, and that of three was decreased by I.C.V. glucose, NaCl and noradrenaline. Collectively, fourteen of twenty-four tested neurones responded to I.C.V. glucose, twenty-six of forty-one tested neurones responded to I.C.V. noradrenaline and eleven of twenty-six tested neurones responded to I.C.V. NaCl. 4. Increase of ambient temperature changed the activity of five e.e.g.-independent neurones. Directions of these activity changes were the same as directions of responses to NaCl; two up, three down. 5. The results suggest two main neuronal groups in the v.m.h.: the e.e.g.-related group is involved in the processing of information about sleep-arousal. The e.e.g.-independent group contributes to the long-term processing of information concerned with the regulation of the internal environment such as glucose level, osmotic pressure, NaCl level, the trigger mechanism for feeding, ambient temperature, food preference, etc.

Action Potentials↗
PubMed1987

Sex-related differences in fever development of rats.

Lipopolysaccharide (LPS) or partially purified endogenous pyrogen (EP) was injected intravenously into rats of both sexes to induce fever. In LPS fever, which was easily produced in 24-h dehydrated rats with an intravenous injection of LPS, the female rats showed an attenuated febrile reaction as measured by both the maximum increase of rectal temperature (Tre) and the thermal response index (TI). Although castrated female rats showed the same magnitude of febrile reaction to that in normal female rats, castrated male rats had less of a febrile response than normal male rats. During EP fever, the maximum increase of Tre and TI between the male and female rats was also observed to be different. However, castration of rats of both sexes did not affect the febrile reaction to intravenous injection of EP. Ten-week-old female rats, treated by a subcutaneous injection of testosterone propionate on the 1st day after birth, produced a similar magnitude of febrile reaction to that in the normal male rats that were comparable in age. It is concluded that there are sex-related differences in fever development, due both to EP production and structural sexual differences in the central nervous system pathways regulating fever.

Animals↗
PubMed1987

Effects of endogenous pyrogen and prostaglandin E2 on hypothalamic neurons in guinea pig brain slices.

To investigate the direct effects of endogenous pyrogen (EP) and prostaglandin E2 (PGE2) on the activity of neurons in the preoptic and anterior hypothalamic (PO-AH) region, single-unit activity was recorded from brain tissue slices prepared from the PO-AH region of guinea pigs. When EP was applied into the perfusate 18% of warm-responsive neurons decreased their activity, and 23% of warm-responsive neurons increased their activity. Most of the thermally insensitive neurons did not respond to EP. PGE2 inhibited 29% of warm-responsive neurons and facilitated 15% of them. Moreover, when EP and PGE2 were applied to the same neurons at different times, the same directions of changes in neuronal activity were observed in 72% of total neurons examined. These results suggest that EP and PGE2 change the neuronal activity of the thermoresponsive neurons in the PO-AH region involved in fever induction. However, by these results, the direction of neuronal response induced by these substances could not be generally categorized based on the thermoresponsiveness of the individual neuron.

Animals↗
PubMed1987

Functional relations among inferotemporal cortex, amygdala, and lateral hypothalamus in monkey operant feeding behavior.

Neural activity in either the amygdala (AM) or lateral hypothalamus (LHA) was examined while monkeys obtained food as a reward for operant bar pressing. Neurons in the AM were tested before, during, and after reversible cooling of the inferotemporal cortex (ITCx). LHA neurons were tested similarly except that the cooling probe was located in the AM. Cooling probes were chronically implanted bilaterally over the dura of the anterior ITCx in one monkey and in the lateral part of the AM in two monkeys. The activity of 43 AM neurons was analyzed. Before ITCx cooling, each AM neuron was classified into one of four groups based on its response pattern: 6 neurons responded primarily to the sight of food, 11 responded primarily to the sight of nonfood objects, 21 responded to the sight of both food and nonfood (arousal related), and 5 neurons did not respond. ITCx cooling changed the spontaneous firing rate of 15 AM neurons (2 increased, 13 decreased). Responses to the sight of food and/or nonfood of two food-related, four nonfood-related, and seven arousal-related neurons were depressed, and responses of two nonfood-related and three arousal-related neurons were enhanced. Of 17 neurons that were normally food or nonfood specific, 8 became nondiscriminative during ITCx cooling. The activity of 55 LHA neurons was tested. Of these, 22 were food related, 6 responded primarily during ingestion, 22 were arousal related, and 5 did not respond. AM cooling changed the spontaneous firing rates of 21 LHA neurons (12 increased, 9 decreased). Visual responses of nine food-related neurons and two arousal-related neurons were depressed by AM cooling. Ingestion-related responses in the AM (3 of 6 food-related neurons) were not affected by ITCx cooling, but responses of three ingestion-related LHA neurons (3/6) were depressed by AM cooling. The data suggest that dynamic interactions among the ITCx, the AM, and the LHA are important in discriminating between food and nonfood, and, consequently, in the stimulus-reinforcement process, i.e., recognition of reward or no reward. The results are discussed in terms of known anatomical data and behavioral evidence from earlier lesion experiments.

Amygdala↗
PubMed1987

Central sites involved in lateral hypothalamus conditioned neural responses to acoustic cues in the rat.

1. Unit activity in the lateral hypothalamus (LHA) of the rat was recorded during discrimination learning of cue-tone stimuli (CTS) predicting glucose (CTS1+) or intracranial self-stimulation (ICSS) (CTS2+) as positive reinforcement or electric shock (CTS1-) or tail pinch (CTS2-) as negative reinforcement. The same action, licking, was used as the behavioral response to all stimuli. Procaine hydrochloride, a local anesthetic, was microinjected into the ventral tegmental area (VTA) and the amygdala (AM). LHA neuron responses and licking were analyzed to investigate the afferent input pathway(s) responsible for LHA neural responses to conditioning CTSs in positive reinforcement and to identify the central site involved in CTS learning. Although the animals were restrained, there was no respiratory, cardiac rate, or blood pressure evidence of stress. The headholder was specially designed in our laboratory to avoid pain or discomfort to the animal. The subjects would often, after the first few sessions, voluntarily enter into position in the apparatus, presumably to obtain the reward available during the experiments. 2. In positive reinforcement, a rat was rewarded by 5 microliters of glucose or ICSS when it licked a spout. The rat licked for glucose after CTS1+ or for ICSS after CTS2+. In negative reinforcement, an aversive stimulus, either electric shock or tail pinch, was applied if the rat did not lick the spout. The electric shock and tail pinch were maintained weak enough to produce an avoidance ratio less than 20-30%, averaged in all trials. The rat licked to avoid electric shock after CTS1- or tail pinch after CTS2-. 3. Of 271 LHA neurons analyzed, 202 (74.5%) responded to either or both rewarding and aversive stimuli. The number of neurons that responded to only rewarding stimuli was relatively large (105/271), and the number that responded similarly to both rewarding and aversive stimuli was small (29/271). The effects of both glucose and ICSS, and the effects of both electric shock and tail pinch, were usually similar in neurons analyzed for both rewarding and aversive stimulation. Of 271 neurons, 173 responded differentially to rewarding and aversive stimuli. 4. Neural and behavioral responses were recorded before, during, and after local anesthesia of the VTA in 15 rats and of the AM in 14 rats. Injections of 0.3-0.8 microliters of 5% procaine hydrochloride or 0.9% saline were made at a rate of 0.3 microliters/min through guide cannulae chronically implanted in the VTA and AM, ipsilateral to the recording and ICSS sites in 29 rats that self-stimulated.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗
PubMed1987

A comparison of the inhibitory effects of roxatidine acetate hydrochloride and cimetidine on cytochrome P-450-mediated drug-metabolism in mouse hepatic microsomes and in man in vivo.

The inhibitory effects of roxatidine acetate hydrochloride (ROX), a new H2-receptor antagonist, on the oxidative drug-metabolizing enzyme system in mouse hepatic microsomes and in man in vivo were compared with those of cimetidine (CIM). CIM markedly inhibited testosterone 6 beta-, 7 alpha- and 16 alpha-hydroxylase, aminopyrine N-demethylase and aniline hydroxylase activities in mouse hepatic microsomes with inhibition constants (Ki) of 0.2-3.49 mM. ROX exhibited much weaker inhibitory effects on each enzyme activity with 12 to 100-fold higher values of Ki than those of CIM. CIM gave type II difference spectra with dissociation constants (Ks) of 10.4 and 111 microM while ROX gave reverse type I difference spectra with Ks of 55.6 microM. The ratio of 6 beta-hydroxycortisol (6 beta-OHF) to 17-hydroxy corticosteroids (17-OHCS) in urine, used as an indicator of oxidative drug-metabolizing capacity in man, was decreased by 25-35% of the original level on 1-3 d after oral treatment with 800 mg/d of CIM. The ratio was not significantly changed during oral treatment with 150 mg/d of ROX. These results indicate that ROX exhibits a lower affinity for cytochrome P-450 and a lower inhibitory potency on the drug-metabolizing enzymes in hepatic microsomes than does CIM.

Aminopyrine N-Demethylase↗
PubMed1987

Comparative study of tiapride and neuroleptics with anti-dopamine activity on convulsive seizure in mice.

The effects of tiapride on the convulsive seizures induced by pentylenetetrazole, strychnine, picrotoxin and bemegride, and on electric seizure are reported and compared with those of sulpiride, chlorpromazine, haloperidol and reserpine. The number of deaths and intensity of convulsion increased dose-dependently and also with the increase in amplitude of electric shock. Tiapride and a similar compound, sulpiride, did not affect these seizures, whereas chlorpromazine potentiated strychnine-induced and electric seizure. Haloperidol and reserpine potentiated electric seizure, and chlorpromazine and reserpine tended to potentiate bemegride-induced seizure. Reserpine also tended to potentiate pentylenetetrazole-induced seizure. These results suggest that tiapride would be clinically safer than other drugs with anti-dopamine activity, except for sulpiride.

Animals↗
PubMed1987

Contribution of prostaglandin E2 to bradykinin-induced contraction in rabbit urinary detrusor.

Bradykinin (100 pM to 1 microM) contracted the rabbit urinary detrusor in vitro. The sensitivity to bradykinin was about 1000 times higher than that to acetylcholine (ACh) on a molar basis. The contractile response to bradykinin was unaffected by atropine, diphenhydramine, FPL-55712, methysergide, prazosin or tetrodotoxin, indicating that the contraction was not mediated via the release of ACh, histamine, peptide leukotrienes, serotonin or catecholamine. The bradykinin-induced contraction was, however, inhibited by indomethacin (5 microM), a cyclooxygenase inhibitor. Caffeic acid (10 microM), a lipoxygenase inhibitor, did not affect the contraction. Bradykinin (1 nM to 100 nM) stimulated the release of prostaglandin E2 from the detrusor in a concentration-dependent manner, and the release was abolished by treatment with indomethacin (5 microM). Prostaglandin (PG) E2 contracted the urinary detrusor with an EC50 of about 0.1 microM. Adenosine 5'-triphosphate (ATP), a stimulator of PG synthesis, also contracted the muscle with an EC50 of about 100 microM. [14C]Arachidonic acid was converted to PGE2 and F2 alpha when it was incubated with the 700 X g supernatant of the muscle homogenate. However, neither bradykinin nor ATP stimulated the PG synthesis in the supernatant. These results showed that bradykinin and ATP did not affect the cyclooxygenase and/or PG degradation system. On the other hand, when the intact detrusor muscle was incubated with [14C]arachidonic acid, bradykinin and ATP stimulated the PG synthesis, and the stimulated synthesis was inhibited by indomethacin. Mepacrine, a phospholipase A2 inhibitor, more potently inhibited the bradykinin- and ATP-induced contractions than the ACh-induced one.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1987

Involvement of endogenous noradrenaline release in methylene blue-induced contraction of isolated rabbit aorta.

The vasocontractile response to methylene blue (Meb) was investigated in isolated rabbit aorta. Meb (1-100 microM) induced a slowly developing contraction after a long latency in rabbit aortic strip. The maximal contraction was obtained by 50 microM Meb, which corresponded to 1 microM noradrenaline (NA)-induced contraction. Once the maximal contraction was induced by Meb, the strip completely lost the contractile response to a further application of Meb. The usual NA-induced contraction, however, could be observed in such a Meb-insensitive aortic strip. Meb-induced contractions were not affected by atropine, diphenhydramine, methysergide, indomethacin, nordihydroguaiaretic acid and removal of endothelial cells from the aortic strip, but they were abolished by prazosin. In aortic strips from rabbits pretreated with reserpine (3.0 mg/kg, i.m.) for a day, Meb failed to induce contraction. Meb evoked the [3H] release from [3H]NA-preloaded aortic strips. In high performance liquid chromatographic analysis, a considerable amount of NA was found in the bathing fluid of the aortic strip in the presence of Meb. In addition, Meb pretreatment inhibited [3H]NA uptake by the aortic strip and abolished the contractile response to an electrical stimulation of adrenergic nerve terminals. Although Meb decreased the basal level of cyclic GMP in the aortic strip, Meb-induced [3H]NA release from the aortic strip was not affected by 8-bromo cyclic GMP. These results suggest that Meb-induced contraction of rabbit aorta is due to the release of endogenous NA from its storage pools of intramural adrenergic nerves through an independent mechanism of its cyclic GMP lowering effect. In addition, incubation of aortic strips with Meb resulted in depleting the storage NA and blocking the nerve function, suggesting that Meb might be useful for a pharmacological tool as an adrenergic neuron blocking agent in vitro.

Animals↗
PubMed1987

Effect of long-term dosing with tiapride on brain dopamine receptors and metabolism in rats. Comparative study with sulpiride and haloperidol.

The effects of long-term dosing with tiapride for 21 days on barin dopamine receptors and dopamine turnover were compared with those of sulpiride and haloperidol. Haloperidol caused an increase in both antagonist (3H-spiperone) labeled receptors and agonist (3H-N,n-propylnorapomorphine) labeled ones, whereas tiapride acted on the agonist binding sites and sulpiride acted on the antagonist binding sites. The increases induced by sulpiride were only observed in the striatum, while those induced by tiapride and haloperidol were observed in both the striatum and limbic area. Dopamine and dopamine metabolites in the brain tissues were measured at 2 hr and 3 days after long-term dosing with the drugs as an indicator of dopamine turnover. They were higher at 2 hr and lower at 3 days than those of the saline treated controls; however, the increase at 2 hr was much less than that after single acute dosing with drugs. This suggested that all drugs induced tolerance with regard to dopamine turnover. In these studies, tiapride and sulpiride were less active than haloperidol in the effects on brain dopamine receptors and dopamine turnover. This generally weaker activity of sulpiride and tiapride suggest that the benzamide drugs have fewer side effects such as a tardive dyskinesia, than does haloperidol, even after long-term dosing. Furthermore, a slight difference between the effects of tiapride and sulpiride on the dopamine receptor subtypes in the brain subdivision was suggested.

3,4-Dihydroxyphenylacetic Acid↗