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Biomedical subjects

T Matsumiya

Publications and source records attributed to T Matsumiya.

At least 19 recordsLinked to original sources

Effects of the subcutaneous administration of enkephalins on tail-flick response and righting reflex of developing rats.

The s.c. administration of [Met5]-enkephalin to 10-day-old rats pretreated with the mixture of 3 peptidase inhibitors, amastatin, captopril and phosphoramidon, produced the inhibition of tail-flick response and loss of righting reflex. When infant rats were pretreated with the mixture of any combination of two peptidase inhibitors, however, the change in both the response and the reflex were not produced at all by enkephalin injection, indicating that 3 kinds of enzymes, amastatin-sensitive aminopeptidase(s), captopril-sensitive peptidyl dipeptidase A and phosphoramidon-sensitive endopeptidase 24.11, played an important role in the inactivation of enkephalin after its systemic administration. Additionally, the fact that the two enkephalin-induced effects were more effectively antagonized by naloxone, a relatively selective mu-opioid antagonist, than by naltrindole, a specific delta-antagonist, or by nor-binaltorphimine, a specific kappa-antagonist, showed that these two effects were produced by the interaction of enkephalin with mu receptors. Moreover the involvement of mu receptors in the production of these two effects was shown by the fact that the s.c. administration of [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin, a selective mu agonist, also produced these two effects which were more effectively antagonized by naloxone than by naltrindole or nor-binaltorphimine. Since the magnitude of the two effects induced by enkephalins in 15-day-old rats was significantly lower than that in 10-day-old rats, and the two enkephalin-induced effects were not produced at all in 20-day-old rats, a maturation-induced decrease in the permeability of the blood-brain barrier against opioid peptides was indicated.

Aging

Detection and identification modes for the highly sensitive and simultaneous determination of various biogenic amines by coulometric high-performance liquid chromatography.

Detection and identification modes for the rapid, selective, highly sensitive and simultaneous determination of catecholamines, indoleamines and related metabolites by high-performance liquid chromatography (HPLC) with series of coulometric working electrodes (CWE) were investigated. Five detection modes were examined: (1) oxidative single mode using a single CWE, (2) oxidative screen mode using a series of two CWE, (3) redox mode using a series of two CWE, (4) redox-reductive screen mode using a series of three CWE and (5) redox-reductive screen mode using a series of four CWE. For the highly sensitive detection of catechol compounds, oxidative single, redox and redox-reductive screen modes were suitable. Oxidative single and oxidative screen modes were better than the other modes for indole and o-methylated catechol compounds. For the selective detection of these compounds, however, the redox-reductive screen mode was best. The specific ratio obtained in HPLC with the redox or redox-reductive screen mode is useful as an index for identification purposes. These findings suggest that HPLC with the redox-reductive screen mode of detection is applicable to neuroscience studies.

3,4-Dihydroxyphenylacetic Acid

Agonist and antagonist actions of buprenorphine on three types of opioid receptor in isolated preparations.

Both agonist and antagonist actions of buprenorphine on isolated preparations were studied. The Ke (equilibrium dissociation constant) values of both naloxone and Mr 2266 [(-)-2-(3-furylmethyl)-5, 9-diethyl-2'-hydroxy-6,7-benzomorphan] against buprenorphine and the ratio of IC50 (concentration of the drug to produce 50% inhibition of the twitch) value of buprenorphine after to before exposure of mouse vas deferens to beta-FNA (beta-fumarate methyl ester derivatives of naltrexone), an irreversible mu antagonist, suggest that buprenorphine acts as both a mu and kappa agonist on mouse vas deferens. The agonist effect of buprenorphine at relatively high doses on guinea-pig ileum and mouse vas deferens and the negative agonist effect on both rat and rabbit vas deferens indicate that buprenorphine acts as a partial agonist on isolated preparations. The Ke values of buprenorphine show that buprenorphine has about equal antagonist effectiveness against a mu and kappa agonist with approximately five-fold lower effectiveness against a delta agonist. The possible mechanisms for the several characteristic actions of buprenorphine on guinea-pig ileum such as the slow onset of action, the increased magnitude of inhibition after washing the tissue, the negative elimination of the inhibition by either washing the tissue or the naloxone administration, and the negative elimination of the antagonist action by washing the tissue were discussed.

Animals

The enhancing effects of amastatin, phosphoramidon and captopril on the potency of [Met5]-enkephalin in rat vas deferens.

The enkephalin-inactivating enzymes in rat vas deferens were studied by using the relatively specific inhibitor of each enzyme. The results showed that the rat vas deferens, like the other three preparations, guinea-pig ileum, mouse vas deferens and striatal membranes of guinea-pig brain, which had been investigated previously, contained three distinct enkephalin-hydrolyzing peptidases. Additionally, the enkephalin-hydrolyzing aminopeptidase, endopeptidase-24.11 and peptidyl dipeptidase A in rat vas deferens were found to be inhibited maximally with 1 microM of amastatin, 1 microM of phosphoramidon and 1 microM of captopril, respectively. In contrast to these three enzymes, both L-tyrosyl-L-tyrosine-sensitive dipeptidyl aminopeptidase and D-phenylalanine-sensitive carboxypeptidase were suggested not to be involved significantly in the inactivation of exogenously given enkephalin in rat vas deferens. The characteristics of the enkephalin-degradative enzymes in rat vas deferens were discussed in terms of their similarities to and differences from those in the other preparations.

Animals

Inactivation of [Leu5]-enkephalin in three isolated preparations: relative importance of aminopeptidase, endopeptidase-24.11 and peptidyl dipeptidase A.

Enkephalin had been shown to be almost exclusively hydrolyzed by three peptidases in the previous studies. In the present investigation, the relative importance of three enzymes in the inactivation of [Leu5]-enkephalin was examined in three isolated preparations. Results showed that amastatin-sensitive aminopeptidase played the greatest role in both guinea-pig ileum and rat vas deferens while it played the similar role to either phosphoramdidon-sensitive endopeptidase-24.11 or captopril-sensitive peptidyl dipeptidase A in mouse vas deferens.

Animals

The effects of morphine, naloxone and capsaicin on C-fiber reflex and heat evoked discharge in acute spinal cats.

The electrophysiological effects of morphine, naloxone and capsaicin were studied on c fiber reflex and heat evoked discharge in adult spinal cats. C fiber reflex was recorded from the L7 Ventral root at the time of superficial peroneal nerve electric stimulation. Heat evoked discharge was recorded from the L7 ventral root at the time of hind paw heating. The drugs were injected slowly into the right cephalic vein. Our results can be summarized as follows: morphine depressed the excitatory neuronal activity of capsaicin; morphine followed by capsaicin was antagonized by 0.4 mg/Kg of naloxone; at the c fiber reflex, 2 mg/Kg of morphine depressed the neuronal activity; and at heat evoked discharge, 4 mg/Kg of morphine depressed the neuronal activity. These findings suggest that morphine depressed the effect of capsaicin and this effect was antagonized by naloxone. At the c fiber reflex, morphine was more sensitive than at heat evoked discharge.

Animals

The effect of naloxone on C-fiber reflex in cats.

The specific opiate antagonist naloxone rapidly reverses hypotension caused by endotoxin, hypovolemia and spinal transection. The fact that naloxone appears to act as a causative level to improve shock pathophysiology, as well as its extensive clinical use for opiate overdose, makes this drug a particularly clinical use for opiate overdose, makes this drug a particularly attractive potential therapeutic agent for the treatment of shock in humans. The electrophysiological effects of naloxone were studied on c-fiber reflex in spinal and intact cats. The drugs were injected in to the right cephalic vein. Results can be summarized as follows: Naloxone in the intact cat had a more pronounced facilitating effect than in the spinal cat. Naloxone given as a one shot injection was more potentiating than naloxone given as a 5 minute injection. Naloxone antagonized the facilitation of a small dose of ketamine-HCL in the intact cat and also the depression of a large dose ketamine-HCL. Naloxone antagonized capsaicin on c-fiber reflex. This result supports that naloxone has the antagonizable inhibitory effect of substance-P. Naloxone for the first injection had an effective response but additional naloxone did not facilitate the c-fiber reflex.

Animals

The effect of capsaicin on C-fiber reflex and heat evoked discharge in the acute spinal cat.

The effects of capsaicin were studied electrophysiologically on C-fiber reflex and heat-evoked discharge in adult spinal cats. The results can be summarized as follows: 1) 125 micrograms/Kg of capsaicin, administered intravenously, induced an increase in spontaneous discharge in the L7 ventral root; 2) 250 micrograms/Kg of capsaicin, administered intravenously, induced an increase in the C-fiber reflex response; 3) 125 micrograms/Kg of capsaicin, administered intravenously, induced an increase in the heat-evoked discharge; but 4) 25 micrograms/Kg of capsaicin, administered through the femoral artery, did not show significant alteration of the heat-evoked discharge. These findings suggest that capsaicin which produced a release of substance-P from primary afferent nerves may principally act on C-fiber and A delta-fiber. Capsaicin was much more effective on the heat-evoked discharge than on the C-fiber reflex when administered intravenously.

Afferent Pathways

The effects of droperidol and diazepam on the neural excitation of ketamine hydrochloride.

The effects of neuroleptics (droperidol and diazepam) were studied on the neural excitation by ketamine hydrochloride by means of the c-fiber reflex, in the spinal cat and the intact cat. Results can be summarized as follows: 1) Ketamine hydrochloride 125-500 micrograms/Kg i.v. facilitated the neural activity on the c-fiber reflex of the intact cat, but it depressed that of the spinal cat. 2) Droperidol 50-250 micrograms/Kg i.v. and diazepam 50-250 micrograms/Kg i.v. did not influence the neural activity on the c-fiber reflex of the intact cat, but it depressed that of the spinal cat. 3) Droperidol 125 micrograms/Kg i.v. followed by ketamine hydrochloride 125 micrograms/Kg i.v. facilitated the neural activity of the intact cat c-fiber reflex. 4) Diazepam 50 micrograms/Kg i.v. followed by ketamine hydrochloride 250 micrograms/Kg i.v. did not influence the neural activity of the intact cat c-fiber reflex. These data suggested that the neural excitation of ketamine hydrochloride was depressed by diazepam and that a small dose of droperidol did not depress the neural excitation of the intact cat.

Animals

The choice of opiate receptor subtype by neo-endorphins.

The choice of opiate receptor subtype by alpha- and beta-neo-endorphin was studied in isolated preparations. Neo-endorphins had significant inhibitory actions on the electrically evoked contractions of guinea-pig ileum, mouse vas deferens and rabbit ileum as well as on the rabbit vas deferens which had been shown to contain kappa-receptors exclusively. Mr 2266, a relatively specific kappa-receptor antagonist, was more effective than naloxone, a relatively mu-receptor antagonist, to antagonize the agonist actions of neo-endorphins in either the guinea-pig and rabbit ileum or in the rabbit vas deferens. By contrast, in the mouse vas deferens, the effectiveness of Mr 2266 to antagonize the agonist actions of neo-endorphins was low and similar to that of naloxone. The potencies of neo-endorphins relative to that of ethylketocyclazocine, a representative kappa-receptor agonist, in the guinea-pig ileum were similar to those in the rabbit ileum but were significant different from those in the mouse vas deferens. The data indicate that neo-endorphins act as kappa-receptor agonists in either the guinea-pig and rabbit ileum or in the rabbit vas deferens while in the mouse vas deferens they act on opiate receptor subtypes other than kappa- and mu-receptors.

Animals

Effects of Peripheral monoamines on the monosynaptic reflex neuronal activity of acute spinal cats.

The monosynaptic reflex (MSR) neuronal activity of acute spinal cats was affected not only by monoamine levels in the central nervous system (CNS) but also by peripheral physiological changes, i.e. blood pressure and the temperature of the paraffin pool. Therefore, this report discusses the effects of peripheral monoamines, especially dopamine (DA) or norepinephrine (NE), on the MSR amplitude of acute spinal cats. The results were as follows: 1. Intravenous injections of DA or NE, which did probably not enter the CNS because of the blood-brain barrier, increased MSR neuronal activity. 2. These effects were blocked by the DA receptor antagonist, haloperidol, and the alpha-receptor antagonist, phenoxybenzamine, but not by the beta-receptor antagonist, propranolol. 3. This effect of NE was about 20-fold stronger that that of DA. 4. Larger doses of both amines caused increases in the blood pressure. These results suggested that most hypertensive drugs which cause increases in levels of NE influence the stimulation MSR neuronal activity.

Animals

Anti-alcohol action of hepaticoactivator (NKK-105) on motoricity and EEG in experimental animals and man.

The effects of a hepaticoactivator, diisopropyl 1, 3-dithiol-2-ylidene malonate (NKK-105), on motoricity and EEG were observed int he rat, mouse, cat and man. NKK-105 suppressed the effects of ethanol (1,000-3,000 mg/kg, p.o., in mice and rats), e.g. the blood alcohol concentration of NKK-105 treated subjects was significantly lower than that of untreated controls. NKK-105, in 100-300 mg/kg p.o. doses, significantly extended the clinging time on a glass rod, and the swimming time. Results indicate that NKK-105 inhibits the effects of alcohol, possibly by hepatic action, and to a lesser extent (neuro) motor activity, by reducing temulence. NKK-105 clearly exhibited anti-alcohol action (metabolic facilitory action) on EEG activity in experiments on cats and man. Almost complete blocking of alcohol action occurred in acute and chronic cats after NKK-105 (100 mg/kg, p.o., or 5-10 mg/kg , i.v.) treatment. It especially inhibited increased amplitude and/or increased slow components in cat neocortex recordings. Most human subjects showed similar results. It is concluded that the anti-alcohol action of NKK-105 seen in the EEG seems to be primarily a liver function, and secondarily a (neuro) motor function.

Animals