Biomedical subjects
Publications and source records attributed to M Ukai.
The effects of naltrexone on the behavior in mice were investigated by using a multi-dimensional behavioral analyser. Within 15 min following observation, naltrexone preferentially suppressed the linear locomotion at the 10 and 30 mg/kg doses. The results suggest that naltrexone selectively disrupts the linear locomotion without affecting other behaviors in mice.
Dynorphin-(1-17) (dynorphin A) significantly reduced the linear locomotion, rearing and grooming behaviors in mice using a newly devised multi-dimensional behavioral analyser. The behaviors inhibited by dynorphin A were dose-dependently antagonized by prior treatment with naloxone. The results suggest that dynorphin A-induced behavioral depression is mediated via opioid receptors in the mouse brain.
The effects of intracerebral injection of dynorphin-(1-13) on spontaneous locomotor activity were investigated by using a newly devised multi-dimensional behavioural analyser based on a capacitance system. With this equipment, nine different measures of behavior exhibited by the mouse can be recorded. It was found that dynorphin-(1-13) (0.3 and 1 microgram) produced a significant increase in the linear locomotion recorded on the 1/1 and 1/2 counters. In addition, dynorphin-(1-13) (0.3 micrograms) significantly increased the grooming behavior recorded on the 1/16 counter. As the dynorphin-(1-13)-induced behavioural effects were reversed by pretreatment with relatively small doses of naloxone (0.5, 1 and 2 mg/kg), the dynorphin-induced increases in linear locomotion and grooming are probably mediated through opiate receptors in the brain.
The effect of the left anterior descending (LAD) coronary artery ligation on myocardial cyclic nucleotides and the role of these nucleotides in the development of ventricular fibrillation (VF) were studied in 135 mongrel dogs by means of sequential punching biopsies from the left ventricle. VF occurred in 50% of the non-premedicated groups. Significant increases of cyclic AMP (c-AMP) concentrations in the ischemic zone were observed after the ligation in VF group. C-AMP concentrations in the ischemic zone were significantly higher after the ligation compared with the border and non-ischemic zone as well as with the non-VF group. They also increased significantly from 30 sec before the onset of VF compared with 2 to 25 min before. No significant change was observed in the control group. In 41 dibutyryl cyclic AMP (DBc-AMP) premedicated dogs, the incidence of VF significantly increased, and c-AMP concentrations were significantly higher than in the non-premedicated group before and after the ligation. They were significantly higher in the ischemic zone 10, 15 and 20 min after the ligation than in the non-ischemic zone. There was a discrepancy of c-AMP concentration between the ischemic zone and the non-ischemic zone in VF induced group, whether DBc-AMP was premedicated or not. Significantly decreased cyclic GMP (c-GMP) levels in the ischemic and the non-ischemic zone were observed after the ligation. C-GMP concentrations with the DBc-AMP premedicated were significantly lower after the ligation compared with the non-premedicated group.(ABSTRACT TRUNCATED AT 250 WORDS)
An investigation was made as to the effects of an intracerebral injection of morphine, endorphins and [des-tyrosine1]-gamma-endorphin (DT gamma E) on spontaneous locomotor activity in mice. This was done by exploiting a newly devised multi-dimensional behavioral analyser with a capacitance system. This apparatus simultaneously recorded nine different degrees of behavior (1/1, 1/2, 1/4, 1/8, 1/16, 1/32, 1/64, 1/128 and 1/256) according to the movement sizes in mice. Within 15 min after injection, gamma-endorphin (5 and 10 microgram), leucine-enkephalin (200 micrograms) and methionine-enkephalin (100 micrograms) produced a significant increase in the 1/1 size of movement. Fifteen to 30 min after injection, the movement patterns induced by morphine (40 micrograms) and DT gamma E (40 micrograms) became similar, although morphine (40 micrograms) caused a significant decrease in the 1/1 and 1/2 sizes of movement. beta-Endorphin (2 micrograms) significantly decreased most of the movement sizes for 30 min compared with saline-treated group. [D-alanine2]-methionine-enkephalinamide (20 micrograms) significantly decreased almost all the movement sizes within 15 min after injection. The significant alteration in the movement sizes induced by morphine and endorphins except for DT gamma E was antagonized by pretreatment with naloxone (1 mg/kg). These results strongly suggest the qualitative difference in the behavioral effects of each of the opioids and nonopioid.
This study was designed to investigate the relationships of myocardial concentrations of norepinephrine (NE) and cyclic AMP (c-AMP) to the development of ventricular fibrillation (VF) with reference to the effects of a premedication of dibutyryl cyclic AMP (DBC-AMP) and propranolol in dogs with experimental myocardial infarction. Myocardial specimens were obtained serially from the ischemic and the non-ischemic zones by mini-drill biopsy, and NE and c-AMP levels were determined by high-performance liquid chromatography and radioimmunoassay, respectively. Before the occurrence of VF, myocardial NE increased in both the ischemic and the non-ischemic zones, and c-AMP increased significantly in the ischemic zone but did not in the non-ischemic zone. In dogs premedicated with DBC-AMP an increase of c-AMP was observed in both the ischemic and the non-ischemic zones in association with an increased incidence of VF. On the other hand, no significant increase of myocardial c-AMP was observed in both the ischemic and the non-ischemic zones of propranolol-premedicated dogs which were free from VF. A significant increase of myocardial c-AMP in the ischemic zone was observed in dogs which suffered from VF in spite of the premedication of propranolol. The incidence of VF was significantly reduced by 26.5% in dogs pretreated with propranolol. No significant changes in myocardial norepinephrine and c-AMP were observed in dogs which were free from VF throughout the experiments.
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The effects of intracerebral injection of alpha-, beta- and gamma-endorphins on the mouse brain dopamine (DA) metabolism were contrasted in relation to the previously identified patterns of behavior. alpha-Endorphin (20 micrograms) decreased the content of homovanillic acid (HVA) in the striatum, while gamma-endorphin (10 micrograms) the contents of DA, 3,4-dihydroxyphenylacetic acid and HVA. beta-Endorphin (1 and 2 micrograms) had no effects on the mouse DA metabolism in the brain. The changes in the DA metabolism induced by alpha- and gamma-endorphins were readily reversed by the pretreatment with naloxone (1 mg/kg). Results suggested: (1) the patterns of behavior in mice treated with endorphins are mediated by these differences in DA metabolism; (2) changes in DA metabolism induced by alpha- and gamma-endorphins occur via opiate receptors in the mouse brain.
High-pressure liquid chromatography with electrochemical detection is utilized in a procedure for the determination of methionine-enkephalin (MET-ENK), norepinephrine (NE), dopamine (DA), 3, 4-dihydroxyphenylacetic acid (DOPAC) and 3-methoxy-4-hydroxyphenylacetic acid (HVA) in same brain tissue samples. The high degree of selectivity and sensitivity (picomole limits for each component) makes this technique directly applicable to extremely small samples. After optimal conditions had been established, the procedure was employed in the determination of MET-ENK, NE, DA, DOPAC and HVA contents in whole brains, 7 discrete brain areas of mice and rats.
Substance P (SP) and analogs, including 5 nucleoside (ARA or HRA)-peptides, were examined for antidiuretic activity in ethanolized rats. The activity was potent in the analogs embodying the C-terminal hexapeptide, weak in the nucleoside-pentapeptide, and negligible in the nucleoside-tetrapeptide. In addition, the activity was increased by acylation of the hexapeptide. The antidiuretic potencies were also compared with the hypotensive potencies.
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The relationship between the analgesic action of eptazocine and brain catecholamine was investigated by pharmacological and neurochemical methods in comparison with pentazocine (PZC) and morphine (MOR). The analgesic action of eptazocine as determined by the pressure method was decreased by pretreatment with 6-hydroxydopamine (6-OHDA) or disulifram. Eptazocine increased the norepinephrine (NE)level in the brain stem, but decreased the dopamine (DA) level in the cortex. Eptazocine decreased the rates of DA turnover in the cortex and the brain stem and NE turnover in the spinal cord. The analgesic action of PZC was decreased by alpha-methyl-rho-tyrosine ( alpha-MT), disulfiram, 6-OHDA, or reserpine. PZC decreased NE levels in the cortex and the brain stem, and DA level in the striatum. The turnover rates of NE in the brain stem and the spinal cord were increased by PZC. The analgesic action of MOR was potentiated by alpha-MT and attenuated by reserpine or 6-OHDA. MOR decreased NE and DA levels in the cortex and NE level in the brain stem, but increased DA level in the brain stem and NE level in the spinal cord. The turnover rates of NE in the cortex and the brain stem were increased at low doses of MOR, but those of DA in the striatum and NE in the spinal cord were decreased at high dose of MOR. These results suggest that the mechanism of eptazocine-induced analgesia is different from those of PZC and MOR in terms of the relationship to catecholamine neurons.
Isolated rat pancreatic islets were preincubated in a medium with 16.7 mM glucose and incubated with 5.5 mM glucose. Both histamine (100 microM) and neurotensin (100 nM) stimulated glucagon release from the isolated islets, but not insulin release. The stimulation of glucagon release occurred in the presence of 10 and 100 nM neurotensin, while the release of insulin was inhibited in the presence of 1 and 10 nM neurotensin. The neurotensin-induced glucagon release was completely inhibited by 1 mM metiamide, an histamine H2-receptor antagonist, added to the incubation medium and not inhibited by 1 mM diphenhydramine, an histamine H1-receptor antagonist. The results indicate that the histaminergic mechanism, including the H2-receptor system, may be involved in neurotensin-induced glucagon release from the endocrine pancreas.
The relationship between the analgesic action of eptazocine and brain 5-HT was investigated by pharmacological and neurochemical methods in comparison with pentazocine (PZC) and morphine (MOR). The analgesic effects of eptazocine, PZC, and MOR as determined by the pressure method were decreased by pretreatment with rho-chlorophenylalanine or 5,6-dihydroxytryptamine. The analgesic effects of all three drugs were also diminished by a lesion in the dorsal half of the spinal cord (C5-6) or the raphe magnus. A lesion in the central gray produced a decrease in the analgesic effects of MOR or PZC, but had a weak effect on that of eptazocine. All three drugs increased 5-hydroxyindole acetic acid (5-HIAA) levels in the brain stem, the striatum, and the spinal cord. In addition, eptazocine decreased the 5-HIAA level in the cortex and the 5-HT level in the hippocampus, but increased the 5-HT level in the spinal cord. An increase of 5-HIAA in the cortex and a decrease of 5-HT in the brain stem were observed after PZC-administration. On the other hand, MOR decreased the 5-HT level in the brain stem and striatum. These results suggest that the effects of eptazocine on 5-HT neurons are similar to those of PZC and MOR, but part of the action mechanism of eptazocine is different from those of PZC and MOR.
The effects of intracerebral injection of methionine-enkephalin (met-enk) and leucine-enkephalin (leu-enk) on the behavioral patterns were examined by using multi-dimensional behavioral analyser (Animex II) in relation to the mouse brain monoamine metabolism. The multi-dimensional behavioral analyser which is able to record 9 different measures of behavior exhibited by mice has been used. The results have indicated that met-enk (100 micrograms) and leu-enk (200 micrograms) caused a remarkable but transient increase in the linear locomotion recorded on the counter 1/1. In the biochemical study, it has been found that met-enk (100 micrograms) significantly increases the content of homovanillic acid (HVA) in the striatum. Leu-enk (200 micrograms) has negligible effect on the contents of dopamine (DA), 3,3-hydroxyphenylacetic acid and HVA in the cerebral cortex or the striatum. Met-enk (100 micrograms) and leu-enk (200 micrograms) did not affect the alpha-methyl-p-tyrosine-induced decrease in the content of DA and norepinephrine. Following the injection of met-enk (100 micrograms) and leu-enk (200 micrograms) and leu-enk (200 micrograms) into the cerebral ventricle, the content of 5-hydroxytryptamine in the cerebral cortex was increased but that of 5-hydroxyindoleacetic acid was not. Neither met-enk nor leu-enk influenced the activity of monoamine oxidase in the brain. These data suggest that, while monoamines in the brain are involved in the behavioral effects of enkephalins, the precise sites and/or mechanisms of enkephalins may differ.
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