Biomedical subjects

Y Misu

Publications and source records attributed to Y Misu.

At least 91 records · Page 5Linked to original sources

PubMed1991

Nanomolar L-dopa facilitates release of dopamine via presynaptic beta-adrenoceptors: comparative studies on the actions in striatal slices from control and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated C57 black mice, an animal model for Parkinson's disease.

Effects of L-DOPA (0.1-10,000 nM) on spontaneous release (Sp), evoked release (S) and tissue content (C) of dopamine (DA) were studied comparatively in superfused striatal slices from control and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated C57 black mice to obtain evidence for L-DOPA-induced facilitation of S via presynaptic beta-adrenoceptors. In control slices, isoproterenol-induced concentration-dependent increases in S were propranolol-sensitive. L-DOPA at 0.1-3 nM tended to increase the S of DA with a concomitant tendency of increases in Sp. L-DOPA at 10-1 x 10(4) nM concentration-dependently increased Sp. L-DOPA at 1-10 microM tended to increase S and 10 microM increased C. In slices from MPTP-treated mice, the absolute amounts of Sp, S and C decreased by half compared to those in control slices. L-DOPA at 3 nM facilitated S without increasing Sp. This facilitation was antagonized by propranolol at 3 nM. L-DOPA at 30 nM decreased S from the peak facilitation, which contrasted with no effect in the control slices. However, 10-100 nM L-DOPA increased Sp more markedly than that in the control slices. L-DOPA at 100 nM increased S and C, which contrasted with no effect in the control slices. In conclusion, nanomolar L-DOPA facilitates the S of DA via presynaptic beta-adrenoceptors at concentrations lower than those required to induce conversion to DA even in striatal slices from the MPTP-treated mice model for Parkinson's disease.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1991

L-dihydroxyphenylalanine methyl ester is a potent competitive antagonist of the L-dihydroxyphenylalanine-induced facilitation of the evoked release of endogenous norepinephrine from rat hypothalamic slices.

Using high performance liquid chromatography with electrochemical detection, we attempted to find among L-dopa-related analogs a competitive antagonist against L-dopa-induced facilitation of impulse (2 Hz)-evoked endogenous norepinephrine (NE) release from rat hypothalamic slices. At the first screening in the presence of cocaine and 3-hydroxybenzylhydrazine (NSD-1015), a L-aromatic amino acid decarboxylase inhibitor, L-dopa (1-100 nM) concentration-dependently facilitated NE release. L-dopa (1 microM) reduced NE release. D-dopa, L-phenylalanine, 3-O-methyl-dopa, 3,4-dihydroxyphenylacetic acid or L-dopa-phosphate at 1 to 1000 nM, and carbidopa (1-10 nM), did not mimic L-dopa. L-dopa methyl ester (0.3-10 nM) concentration-dependently decreased NE release, suggesting that it is antagonistic, whereas L-threo-3,4-dihydroxyphenylserine (0.001-1 nM) concentration-dependently mimicked L-dopa. At the second screening in the additional presence of S-sulpiride, L-dopa (1-1000 nM) concentration-dependently facilitated NE release. Maximum effect was seen at 0.3 to 1 microM. Pretreatment with carbidopa (0.1-10 nM) or L-dopa phosphate (0.01-0.1 nM) was somewhat antagonistic. L-Dopa methyl ester (3-30 nM) in a concentration-dependent manner shifted the concentration-facilitation curve for L-dopa to the right: Schild plots gave a straight line with a slope of 1.00 and pA2 was 8.9, whereas l-propranolol (1-100 nM) concentration-dependently reduced maximal effect of L-dopa without rightward shift of the curve. L-Dopa methyl ester and some large neutral amino acids inhibited uptake of [3H]-L-dopa into slices in the presence of NSD-1015.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Evidence that endogenous catecholamines are involved in alpha 2-adrenoceptor-mediated modulation of the aortic baroreceptor reflex in the nucleus tractus solitarii of the rat.

Microinjections of alpha-methylnoradrenaline and tyramine into the rat nucleus tractus solitarii (NTS) potentiated the depressor and bradycardiac responses to aortic nerve stimulation whereas yohimbine injected similarly inhibited them. NTS pretreatment with yohimbine inhibited the baroreflex potentiation effects of alpha-methylnoradrenaline and tyramine whereas intraventricular pretreatment with 6-hydroxydopamine inhibited only that of tyramine. These results provide evidence that endogenous catecholamines in the rat NTS are involved in alpha 2 adrenoceptor-mediated modulation of the aortic baroreceptor reflex.

Animals↗

PubMed1990

Nicotine releases stereoselectively and Ca2(+)-dependently endogenous 3,4-dihydroxyphenylalanine from rat striatal slices.

In superfused slices of rat striatum, nicotine-evoked release of endogenous 3,4-dihydroxyphenylalanine (DOPA) was studied in comparison with that of dopamine (DA). (+/-)-Nicotine (0.1-10 microM) constantly and repetitively released DOPA and DA over a similar time course in a concentration-dependent manner. The ratio of DOPA and DA evoked was approximately 1:2-3. The turnover rate of DOPA was about 300 times higher compared to DA. (+/-)-Nicotine (10 microM)-induced DOPA release was mecamylamine (20 microM)-sensitive, Ca2(+)-dependent and tetrodotoxin (0.3 microM)-insensitive. The (+)-isomer induced no DOPA release. These characteristics of DOPA release were almost the same as those of DA. Nicotine evokes endogenous DOPA via nicotinic cholinergic receptors in a manner similar to the transmitter DA. These findings further support a probable role of DOPA as a neuroactive substance in the rat central nervous system.

Animals↗

PubMed1990

Evaluation of a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated C57 black mouse model for parkinsonism.

We evaluated neurochemically, behaviorally, and neuropathologically the availability of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated C57 black (BL) mice as a model for Parkinson's disease. The dopamine and 3,4-dihydroxyphenyl acetic acid content in the striatum, measured by high-performance liquid chromatography with an electrochemical detector, decreased by 70% at 10 and 20 days after the withdrawal of MPTP (30 mg/kg, i.p. twice daily for 5 days). During these days, the mice showed a decrease in locomotor activity and exhibited akinesia in both pole and traction tests. Light microscopically, 44% of the MPTP-treated mice showed neuronal degeneration in the substantia nigra 1 month after the withdrawal (damaged group), and 56% showed no change (undamaged group). Morphometric analysis revealed that the number of neurons in the substantia nigra decreased by 33% on the average in both groups. Electron microscopically, an electron-dense degeneration of most neurons was seen in the substantia nigra of the damaged group, and even in the undamaged group, loss of rough endoplasmic reticulum and mitochondrial deformity were seen in 50-70% of the neurons. Electron-dense bodies were seen in the striatum of both groups. These results show the validity of the MPTP-treated C57 BL mice as a suitable model for parkinsonism, including Parkinson's disease.

Animals↗

PubMed1990

Electrical stimulation-evoked release of endogenous aspartate from rat medulla oblongata slices. Effects of inhibitors of aspartate aminotransferase and GABA transaminase.

The effects of aminooxyacetic acid (AOAA), an aspartate aminotransferase (AAT) inhibitor, L-canaline, an ornithine aminotransferase inhibitor, and gamma-acetylenic GABA and gabaculine, both gamma-aminobutyric acid transaminase (GABA-T) inhibitors, on the release of aspartate from slices of rat medulla oblongata and hippocampus were studied. The slices were superfused and electrically stimulated. There was a Ca2(+)-dependent stimulus-evoked release of endogenous aspartate. AOAA (10(-4) and 10(-3) M) decreased the evoked release of aspartate in the medulla oblongata but not in the hippocampus. In addition, AOAA produced a decrease in the spontaneous efflux and tissue content of aspartate in the medulla oblongata. L-Canaline (5 x 10(-5) M), gamma-acetylenic GABA (10(-4) M) and gabaculine (10(-5) M) did not affect the evoked release of aspartate in the medulla oblongata, while these agents produced a decrease in spontaneous efflux and tissue content of aspartate. These findings suggest that AAT participates in the synthesis of transmitter aspartate in the medulla oblongata of the rat. It appears that there are the pools of transmitter aspartate and non-transmitter aspartate in the rat medulla oblongata.

4-Aminobutyrate Transaminase↗

PubMed1990

L-dopa methyl ester antagonizes competitively L-dopa-induced facilitation of noradrenaline release from rat hypothalamic slices.

In rat hypothalamic slices, antagonism by L-DOPA methyl ester and (-)-propranolol against L-DOPA-induced facilitation of endogenous noradrenaline (NA) release was characterized under the inhibition of dopadecarboxylase. L-DOPA at 10 nM to 1 microM facilitated the evoked NA release in a concentration-dependent manner. L-DOPA methyl ester (3, 10 and 30 nM) progressively shifted the concentration-release curve for L-DOPA to the right: Schild plots gave a straight line with a slope of 1.00 and pA2 was 8.9. This antagonistic action was not mimicked by L-phenylalanine, a substrate for L-DOPA transport system. In contrast, 10 and 100 nM propranolol concentration-dependently reduced the maximal effect of L-DOPA without rightward shift of the concentration-release curve. L-DOPA methyl ester is a potent competitive antagonist for the action of L-DOPA, and the recognition site of L-DOPA differs from presynaptic beta-adrenoceptors.

Animals↗

PubMed1990

Carteolol is a useful tool to prove the tonically functioning nature of presynaptic beta-adrenoceptors on peripheral noradrenergic neurons but not on central catecholaminergic neurons.

Effects of carteolol on norepinephrine (NE) release were studied at 2 Hz mainly in rat hypothalamic slices. Isoproterenol at 1 and 10 nM concentration-dependently facilitated NE release. Isoproterenol (10 nM)-induced facilitation was antagonized by 1 and 10 nM dl-carteolol, but not antagonized by 1 nM d-carteolol. dl-Carteolol alone at 1 nM to 10 microM did not inhibit NE release. In brainstem slices, 10 nM isoproterenol also facilitated NE release, and this facilitation tended to be antagonized by 1 nM dl-carteolol. Nanomolar concentrations of carteolol stereoselectively antagonized isoproterenol-induced facilitation of NE release via presynaptic beta-adrenoceptors in rat hypothalamic slices.

Adrenergic beta-Antagonists↗

PubMed1990

L-dopa facilitates the release of endogenous norepinephrine and dopamine via presynaptic beta 1- and beta 2-adrenoceptors under essentially complete inhibition of L-aromatic amino acid decarboxylase in rat hypothalamic slices.

In rat hypothalamic slices, L-aromatic amino acid decarboxylase (AADC) was assayed, and the actions of L-DOPA on impulse (2 Hz)-evoked norepinephrine (NE) and dopamine (DA) release were studied under inhibition of AADC. Slices were incubated with L-DOPA, and DA and NE produced by conversion of the precursor were analyzed by high performance liquid chromatography with electrochemical detection (HPLC-ECD). In the slices, the Km and Vmax of AADC were 131 microM and 122 pmol/min/mg protein, respectively. NSD-1015, an AADC inhibitor, caused a noncompetitive type of inhibition, and the K1 value was 0.086 microM. In the presence of 20 microM NSD-1015, which was expected to cause 99.6% inhibition of AADC, L-DOPA (0.01-100 nM) concentration-dependently facilitated the release of NE from the superfused slices, and the L-DOPA (10 nM)-induced facilitation was antagonized by 100 nM ICI 89,406 and 100 nM ICI 118,551, a selective beta 1- and beta 2-adrenoceptor antagonist, respectively. This action of L-DOPA was not modified by 30 microM tropolone, an inhibitor of catechol-O-methyl-transferase. L-DOPA at 0.01-1 nM similarly facilitated the release of DA. A quantitative analysis revealed that the L-DOPA-induced increase in NE and DA release was much higher by a factor of 3 to 4 orders than was the amount of DA and NE converted from L-DOPA. These results add further support to the hypothesis that L-DOPA itself acts as a neuroactive substance in the rat central nervous system.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1990

Hypotension decreases GABA levels in brainstem regions of the rat.

Concentrations of gamma-aminobutyric acid (GABA) and other amino acids were measured in microdissected areas of the rostral ventro-lateral medulla (RVL), nucleus tractus solitarii (NTS) and caudal ventrolateral medulla (CVL) of the rat, and effects on the amino acid levels, of hypotension induced by hexamethonium and nifedipine were examined. Hexamethonium and nifedipine decreased concentrations of GABA in all the regions studied, while concentrations of glycine, beta-alanine and taurine were not affected by these agents. Both agents caused a prolonged fall in blood pressure. These results strongly suggest that a decrease in blood pressure produces a decrease in GABA levels in the brainstem regions of the rat.

Alanine↗

PubMed1990

Genetically altered brain amino acid metabolism in spontaneously hypertensive rats: a study by using young spontaneously hypertensive rats and renal hypertensive rats.

Previously we demonstrated altered amino acid levels in brainstem regions of adult spontaneously hypertensive rats (SHR). For comparison, in this study, we determined amino acid concentrations in discrete brainstem regions in young prehypertensive SHR and renal hypertensive rats. In prehypertensive SHR, the content of glutamate was increased in the rostral ventrolateral medulla and the caudal ventrolateral medulla, and the content of beta-alanine was decreased in the nucleus tractus solitarii. In renal hypertensive rats, there was no change in glutamate and beta-alanine contents in all the regions. The profiles of contents of glutamate and beta-alanine in the brainstem regions in young SHR but not in renal hypertensive rats are the same as those found previously in adult SHR. Thus, the results of the present study suggest that the altered amino acid metabolism in the brainstem of SHR may be genetically inherent.

Amino Acids↗

PubMed1989

Release by electrical stimulation of endogenous glutamate, gamma-aminobutyric acid, and other amino acids from slices of the rat medulla oblongata.

Evidence was obtained for the release of amino acids by electrical stimulation of slices of regions of the rat medulla oblongata: rostral ventrolateral, caudal ventrolateral and caudal dorsomedial. There was a Ca2+-dependent, tetrodotoxin-sensitive increase in the efflux of aspartate, glutamate, gamma-aminobutyric acid (GABA), glycine, and beta-alanine in all regions examined. There were distinct regional differences in the relative amounts of amino acids released. These results provide evidence for the possible neurotransmitter role of aspartate, glutamate, GABA, glycine, and beta-alanine in these regions of the rat medulla oblongata.

Amino Acids↗

PubMed1989

Evidence for tonic activation of prejunctional beta-adrenoceptors in guinea-pig pulmonary arteries by adrenaline derived from the adrenal medulla.

1. The effects of (+/-)-carteolol 10(-8) M to 10(-6) M, a non-selective beta-antagonist, applied cumulatively, on stimulation-evoked 3H-release at 1 Hz were studied in pulmonary arteries isolated from guinea-pigs. The guinea-pigs were subjected to either bilateral adrenalectomy, adrenalectomy followed by injections of deoxycorticosterone acetate (DOCA) and hydrocortisone, bilateral adrenodemedullation or a sham operation, and then loaded in vitro with [3H]-noradrenaline. 2. Carteolol inhibited 3H-output in arteries from sham-operated animals in a concentration-dependent manner. This inhibitory effect was not found in pulmonary arteries from animals subjected to adrenalectomy or adrenodemedullation. However, DOCA and hydrocortisone pretreatment, did not prevent the disappearance of the carteolol-induced inhibition of 3H-release. 3. Adrenalectomy and adrenodemedullation depleted or markedly reduced the endogenous contents of adrenaline in pulmonary arteries without altering the levels of dopamine and noradrenaline. 4. It is concluded that adrenaline, mainly derived from the adrenal medulla, acts as an endogenous agonist for tonically functioning prejunctional beta-adrenoceptors in guinea-pig pulmonary arteries, probably by being taken up and co-released with noradrenaline.

Adrenal Medulla↗

PubMed1989

Nicotine-induced regional changes in brain noradrenaline and dopamine turnover in rats.

Using high performance liquid chromatography with electrochemical detection, the levels of 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), 3,4-dihydroxyphenylacetic acid (DOPAC) and 3,4-dihydroxyphenylalanine (DOPA) were determined in various brain regions of the rat 1 h after nicotine administration. Nicotine (1 mg/kg, s.c.) produced an increase in MHPG concentrations in the occipital cortex, hippocampus, striatum, hypothalamus, thalamus, midbrain, pons/medulla and cerebellum. This alkaloid at the same dose also caused an increase in DOPAC concentrations in the hypothalamus, thalamus and pons/medulla. The nicotine-induced increase in MHPG and DOPAC concentrations in the brain regions was inhibited by pretreatment with mecamylamine (5 mg/kg, i.p.) but not by hexamethonium (10 mg/kg, i.p.). Nicotine (1 mg/kg, s.c.) produced an increase in DOPA concentrations under DOPA decarboxylase inhibition with NSD-1015 (200 mg/kg, i.p.) in the hypothalamus, thalamus and pons/medulla. These results indicate that nicotine can increase the turnover of noradrenaline and dopamine in various brain regions of the rat and this effect is mediated via activation of central nicotinic receptors.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1989

Effects of acute nicotine on catecholamine turnover in various rat brain regions.

Acute effects of in vivo nicotine application on turnover rates of noradrenaline (NA), adrenaline (AD) and dopamine (DA) in rat occipital cortex, hippocampus, striatum, hypothalamus, thalamus, midbrain, pons/medulla and cerebellum were examined by determining the amine concentrations by high performance liquid chromatography. The regional turnover rates of catecholamines were evaluated by comparing the decline in concentrations produced by blockade of synthesis. Intraperitoneally injected fusaric acid (80 mg/kg), an inhibitor of dopamine-beta-hydroxylase, significantly decreased NA concentration in all eight regions examined, and AD concentration in the hypothalamus and pons/medulla. alpha-Methyl-p-tyrosine methylester (alpha-MPT, 400 mg/kg), an inhibitor of the tyrosine hydroxylase, induced significant and uneven decreases in regional DA concentrations 1 h after the i.p. injection. alpha-MPT also significantly decreased NA concentration in all the regions except the striatum. Subcutaneously injected nicotine 0.4-1 mg/kg significantly enhanced the fusaric acid-induced decline in NA concentrations in the hippocampus and cerebellum. AD decline in the midbrain by fusaric acid was significantly accelerated by nicotine (0.4 mg/kg), but was not affected by a larger dose (1 mg/kg). In the hippocampus, nicotine (1 mg/kg) significantly enhanced the alpha-MPT-induced decrease in NA concentration, while it reduced the decrease in DA concentration. These findings suggest that nicotine can affect the turnover of brain catecholamine in a regionally specific manner.

Animals↗

PubMed1989

Isoproterenol-induced facilitation of norepinephrine release does not primarily involve a local angiotensin II mechanism in guinea pig pulmonary arteries.

We have attempted to clarify whether or not captopril and 1Sar-8Ile-angiotensin II could protect isoproterenol-induced facilitation of norepinephrine release in guinea pig pulmonary arteries loaded with 3H-norepinephrine. Angiotensin I at 1 nM and 30 nM isoproterenol similarly facilitated evoked release of 3H-norepinephrine at 1 Hz. Captopril at 1 microM and 1Sar-8Ile-angiotensin II at 10 nM completely prevented angiotensin I-induced facilitation, whereas these pretreatments produced no effect on isoproterenol-induced facilitation. Isoproterenol-induced facilitation of norepinephrine release does not primarily involve a local angiotensin II mechanism.

1-Sarcosine-8-Isoleucine Angiotensin II↗

PubMed1989

Altered amino acid levels in brainstem regions of spontaneously hypertensive rats.

The contents of glutamate, gamma-aminobutyric acid (GABA), glycine, beta-alanine and taurine in brainstem regions responsible for blood pressure regulation, the rostral ventrolateral medulla (RVL), the nucleus tractus solitarii (NTS) and the caudal ventrolateral medulla (CVL) regions, were determined in spontaneously hypertensive rats (SHR) as compared with Wistar Kyoto rats. In SHR, the content of glutamate was increased in the RVL, NTS and CVL regions whereas GABA and beta-alanine contents were decreased in the RVL and all the regions studied, respectively. There was no difference between WKY and SHR in glycine and taurine contents in all the regions studied. These results provide evidence suggesting alterations of brainstem amino acid metabolism in SHR.

Amino Acids↗

PubMed1988

Involvement of spinal alpha adrenoceptors in mediation of the hypotensive action of guanabenz in rats.

The effects of intrathecal, intracisternal and intravenous injections of yohimbine (10 micrograms) on hypotensive and bradycardic responses to the alpha agonist guanabenz (10 micrograms/kg, i.v.) were studied in anesthetized rats. The depressor response to guanabenz was inhibited by intrathecal pretreatment with yohimbine, while this pretreatment did not affect the bradycardic response to guanabenz. Intracisternal pretreatment with yohimbine inhibited both cardiovascular responses to guanabenz, whereas intravenous pretreatment with yohimbine affected neither. Guanabenz (1 microgram) decreased blood pressure when injected intrathecally but did not affect it when injected intravenously. These results suggest that in rats spinal alpha adrenoceptors are involved in mediation of the hypotensive action of the alpha agonist guanabenz injected systemically.

Animals↗