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Biomedical subjects

T Oka

Publications and source records attributed to T Oka.

At least 1,369 records · Page 76Linked to original sources
PubMed1977

Trypsin as a catalyst for peptide synthesis.

Trypsin-catalyzed syntheses of peptides were performed using various N-acylated amino acid or peptide esters as donors and amino acid derivatives, peptides, or their derivatives as acceptors. The synthesis was almost quantitative under optimal conditions. Considerably more enzyme and a more alkaline pH were necessary for synthesis than hydrolysis. Another very important condition was the concentration of the starting materials; higher concentrations resulted in much better product yields. The nucleophile specificity for synthesis was also important; hydrophobic or bulky amino acid residues were most efficient at the P1' position, and L-proline as well as D-amino acid residues were the worst choices. The synthesis was also dependent on the solubility of the products synthesized; the yield was higher with products of lower solubility. As donor esters, good substrates were all useful. Accordingly, fragment condensation was possible using N-acylated peptide esters and various peptides. The present study suggests that trypsin may become a useful tool for peptide synthesis.

Animals↗
PubMed1977

Role of 5-hydroxytryptamine in morphine-, pethidine-, and methadone-induced hypothermia in rats at low ambient and room temperature.

1 The effect of morphine (10 or 20 mg/kg s.c.), pethidine (25 or 50 mg/kg s.c.) or methadone (4 or 8 mg/kg s.c.) on the body temperature of nontreated and p-chlorophenylalanine-pretreated rats was studied at room (21+/-0.2 degrees C) or low ambient (12+/-0.2 degrees C) temperature. 2 Neither pethidine nor smaller doses of morphine and methadone altered the mean rectal temperature of rats kept at room temperature but larger doses of morphine and methadone produced significant hypothermia. 3 All narcotic analgesics at doses used in the present investigation produced significant hypothermia in rats maintained in a low ambient temperature. The hypothermia was prevented by naloxone (1 mg/kg s.c.). 4 The administration of p-chlorophenylalanine (PCPA, 320 mg/kg i.p.) 48 h before the narcotic injection prevented the fall in body temperature both at room and low ambient temperature. 5 The administration of narcotic analgesics at doses, which when administered by themselves did not alter the body temperature of rats, produced significant hyperthermia in rats pretreated with PCPA. 6 When rats pretreated with PCPA were given 5-hydroxytryptophan (75 mg/kg s.c.) 30 min before narcotic administration, the usual response to narcotics was restored. 7 It appears that pethidine and methadone as well as morphine have both hyperthermic and hypothermic actions in rats and that 5-hydroxytryptamine may be involved in the narcotic-induced hypothermia not only at room temperature but also at low ambient temperature.

5-Hydroxytryptophan↗
PubMed1976

Effects of humoral modulators and naloxone on morphine-induced changes in the spontaneous locomotor activity of the rat.

The s.c. administration of 20 mg/kg of morphine-HCl produced a decrease in the spontaneous locomotor activity (SLMA) of rats. The decrease in SLMA was significantly antagonized by p-chlorophenylalanine (p-CPA). When rats pretreated with p-CPA were given 5-hydroxytryptophan before morphine injection, the marked sedative response to morphine was restored, suggesting that the morphine-induced decrease in SLMA of rats may depend on the release of 5-hydroxytryptamine by morphine. By contrast, the s.c. administration of 5 mg/kg of morphine-HCl produced a significant increase in SLMA of rats. The magnitude of the increase was reduced by atropine, scopolamine or alpha-methyl-p-tyrosine. It appears that both adrenergic and cholinergic mechanisms participate in the increase in SLMA of rats induced by morphine. Both the increase in SLMA produced by 5 mg/kg of morphine and the decrease in SLMA induced by 20 mg/kg of morphine were completely antagonized by the s.c. administration of naloxone-HCl, 0.0625 and 0.25 mg/kg, respectively. Thus, it appears that the receptor with which morphine interacts to produce stimulation is chemically identical with or very similar to the receptor with which morphine combines to induce depression. The former receptors, however, are likely to be located on different neurons from the latter.

5-Hydroxytryptophan↗
PubMed1976

Polyamine transport and metabolism in mouse mammary gland. General properties and hormonal regulation.

Mouse mammary gland has been shown to possess a transport system for spermidine, spermine, and putrescine. The uptake system for sperimidine, as studied in detail on mammary explants in culture is a time-dependent, energy-requiring process which can be stimulated by insulin and prolactin. The stimulatory effect of insulin involves both enhancement of Vmax for spermidine influx and prevention of efflux of the polyamine, whereas prolactin, in the presence of insulin, elicits a greater increase in Vmax for spermidine. Studies are also reported on the effects of temperature, concentration, and various inhibitors on this system. The accumulated spermidine exists virtually in an unchanged form with little metabolic conversion to either spermine or putrescine or to its conjugated form. In contrast, spermine and putrescine, both of which are also taken up by mammary explants, undergo metabolic conversion to spermidine.

Animals↗
PubMed1976

Studies on regulatory factors of ornithine decarboxylase activity during development of mouse mammary epithelium in vitro.

The activity of ornithine decarboxylase increases markedly in a biphasic manner during the hormone-dependent development of mouse mammary epithelium in vitro. The first peak of activity occurring at 3 to 4 hours of culture was elicited by incubating mammary explants in a culture medium without any added hormones, although addition of insulin or prolactin, or both, caused a greater increase. The emergence of the second peak of activity at about 12 hours depended on the actions of both insulin and prolactin. A second increase in activity could also be effected postmitotically by the delayed addition of prolactin. Studies with actinomycin D and cycloheximide suggest that the first increase in enzyme activity may be effected at a post-transcriptional level, whereas a second increase may be at both transcriptional and translational levels. During the first 3 hours of incubation, there was a rapid, transient increase in cyclic AMP concentration in mammary epithelium. The presence of insulin or prolactin in culture did not affect the change in epithelial cyclic AMP concentration. Addition of several derivatives of cyclic AMP, 0.1 to 0.5 mM, as well as prostaglandin E1, a stimulator of adenylate cyclase, resulted in enhancement of the first increase in enzyme activity. The effect of cyclic nucleotide was additive to that of insulin and prolactin and appears to be mediated at a post-transcriptional level. The stimulatory effect of a lower concentration of both the cyclic nucleotide and prostaglandin E1 was augmented by theophylline, an inhibitor of phosphodiesterase. These results may suggest possible involvement of cyclic AMP in the first increase in enzyme activity that occurs in the absence of any added hormones.

Animals↗
PubMed1976

The effect of p-chlorophenylalanine on the pethidine- or methadone-induced decrease in locomotor activity of rats.

Either pethidine HCl (50 mg/kg s.c.) or methadone HCl (8 mg/kg s.c.) produced a prominent decrease in locomotor activity of rats. Pretreatment of rats with p-chlorophenylalanine (p-CPA, 320 mg/kg i.p.) 48 h before the narcotic injection significantly antagonized the activity-decreasing effects of narcotics. When rats pretreated with p-CPA were given 5-hydroxytryptophan (75 mg/kg s.c.) 30 min before narcotic administration, the activity-decreasing response to narcotics was restored. Thus, a decrease in locomotor activity induced in rats by either pethidine or methadone is probably mediated by serotonergic mechanisms.

Animals↗
PubMed1976

Mode of action of penicillins in vivo and in vitro in Bacillus megaterium.

A new system in which the in vivo and in vitro formation of cross-links in the peptidoglycan of Bacillus megaterium can be compared directly has been developed. The method for the determination of the in vivo cross-linking consists of lysozyme digestion of acetylated [(14)C]diaminopimelic acid-labeled cells and Bio-Gel P-6 gel filtration of the digest. The elution profile indicates the cell wall synthesized in vivo consists of highly cross-linked fractions (44%), bisdisaccharide peptide(s) (38%), and disaccharide peptide(s) (18%). The in vitro system showed a high synthetic activity of cross-linked peptidoglycan. The synthesis was inhibited completely by 83.3 mug of ristocetin or vancomycin per ml or 10(-4) M p-chloromercuribenzoate and inhibited only partially by penicillins. The polymerization was stimulated by high concentrations of sucrose, glycerol, amino acids, or dimethyl sulfoxide. The formation of cross-links was inhibited 50% at 0.3 mug of dicloxacillin per ml and 90% at 0.5 mug or more. It was also stimulated by high concentrations of sucrose, glycerol, or dimethyl sulfoxide. Effective concentrations of dicloxacillin on the growth, viability, and morphology of B. megaterium were determined. Sharp inhibition of cross-linking occurred in vivo and in vitro at these effective concentrations, whereas the incorporation of [(14)C]-diaminopimelate into bacterial cells was not affected at all. Cell-bound dicloxacillin reduced severely the degree of cross-linking in the cell wall synthesized after transfer to a dicloxacillin-free medium. Cell wall synthesized in the presence of dicloxacillin showed a higher rate of turnover than did the normal cell wall. Moreover, disaccharide peptide(s) was degraded faster than was bisdisaccharide peptide(s) in dicloxacillin-treated cells. From these observations, the primary target of penicillin action in B. megaterium is discussed in relation to the inhibition of cross-linking, penicillin-binding components, and cell lysis.

Amino Acids↗
PubMed1976

[Effects of l-methyl-5-(O-fluorophenyl)-7-chloro-1,3-dihydro-2H-1,4-benzodiazepin-2-One (ID-540) on operant behavior in rats].

Effects of ID-540, a new benzodiazepine derivative, on operant behavior were studied and compared with those of diazepam in rats for the purpose of determining the characteristics on behavioral pharmacology. Four schedules used were as follows: Fixed interval (FI-60sec) of food reinforcement and differential food reinforcement of low rate (DRL20sec) for positively reinforced behavior, Sidman-type avoidance response for negatively reinforced behavior and conflict behavior induced by simultaneously rewarding with food and punishing with electric shock. In the experiments on FI-60sec schedule, the responses at the early stage (0 approximately 30 min after administration of the drug) were increased by both ID-540 and diazepam at lower doses (0.5 approximately 4 mg/kg p.o.), but inhibited at higher doses (8 approximately 32 mg/kg p.o.). The effect of ID-540 lasted longer than that of diazepam. In the experiments on DRL20sec schedule, neither drug accelerated the responses, but decreased the lever-press response and total number of reinforcements at higher doses (4 mg/kg or more) showing the disturbance of discrimination on time. In Sidman-type avoidance responses, ID-540 did not show any inhibitory effect, thus a neuroleptic-like effect of ID-540 was not demonstrated. In experiments on FI-60sec and Sidman-type avoidance schedules, the effect of ID-540 was not changed by a consecutive administration for 10 days. Conflict behavior is considered to resemble the anxiety states in humans, and in related experiments, ID-540 increased the lever-press response which delivered a food-pellet and an electric shock simultaneously at a dose of 0.0625 mg/kg (i.p.). Change in other behavior was not observed at this dose level. Maximum effect of ID-540 was observed at a dose of 0.5 mg/kg (i.p.). Maximum effect of diazepam on conflict behavior was seen at a dose of 4 mg/kg (i.p.). The potency of ID-540 on conflict behavior was estimated to be about 8 times that of diazepam.

Animals↗
PubMed1976

Effects of narcotic analgesics on serotonin metabolism in brain of rats and mice.

The effects of narcotic analgesics on the brain 5-hydroxytryptamine (5-Ht) and 5-hydroxyindoleacetic acid (5-HIAA) levels of rats and mice were investigated in relation to our preceding data on the effect of humoral modulatorents. The results suggest that morphine accelerates the release of brain 5-HT both in rats and mice, and that neither methadone nor pethidine alters the brain 5-HT and 5-HIAA levels in rats. The morphine-induced increase in brain 5-HT turnover is likely to be involved in the morphine-induced decrease in locomotor activity and hypothermia in rats. The activity-decreasing effects of methadone or pethidine, on the other hand, are mediated by mechanisms different from those which mediate the effects of morphine. In contrast, an increase in brain 5-HT turnover in mice apparently does not play an important role on activity-increasing effects of morphine but rather participates in other pharmacological effects of morphine.

Analgesics, Opioid↗
PubMed1976

Effect of humoral modulators of morphine-induced increase in locomotor activity of mice.

The effect of humoral modulators on the morphine-induced increase in locomotor activity of mice was studied. The subcutaneous administration of 10 mg/kg of morphine-HC1 produced a marked increase in locomotor activity in mice. The morphine-induced hyperactivity was potentiated by scopolamine and attenuated by physostigmine. In contrast, both methscopolamine and neostigmine, which do not penetrate the blood-brain barrier, had no effect on the hyperactivity produced by morphine. Pretreatment of mice with alpha-methyltyrosine (20 mg/kg i.p., one hour), an inhibitor of tyrosine hydroxylase, significantly decreased the activity-increasing effects of morphine. On the other hand, pretreatment with p-chlorophenylalamine (3 X 320 mg/kg i.p., 24 hr), a serotonin depletor, caused no significant change in the hyperactivity. The study suggests that the activity-increasing effects of morphine are mediated by the release of catecholamines from adrenergic neurons in the brain. And the results are consistent with the hypothesis that morphine acts by retarding the release of acetylcholine at some central cholinergic synapses. It is also suggested from collected evidence that the activity-increasing effects of morphine in mice are mediated by mechanisms different from those which mediate the activity-increasing effects of morphine in rats.

Animals↗
PubMed1975

Insulin-unresponsive tissues respond to superactive insulin-like material.

Insulin-like material prepared from insulin-Sepharose stimulates glucose oxidation by isolated diaphragm of C57Bl/6J ob/ob mice, but insulin does not. This material is much more effective than insulin on epididymal fat tissue from these mice. Insulin-like material and insulin are equipotent on the corresponding tissues from lean littermates.

Adipose Tissue↗