Search PubMed⌕ Search

Biomedical subjects

Y Misu

Publications and source records attributed to Y Misu.

At least 109 records · Page 6Linked to original sources
PubMed1988

GABA transaminase inhibitors enhance the release of endogenous GABA but decrease the release of beta-alanine evoked by electrical stimulation of slices of the rat medulla oblongata.

Slices of the rat medulla oblongata were superfused and electrically stimulated. The amount of endogenous GABA, beta-alanine and glutamate release from the slices was determined by high performance liquid chromatography with fluorometric detection. Inhibitors of GABA-transaminase (GABA-T), aminooxyacetic acid (10(-5) M), gamma-acetylenic GABA (10(-4) and 10(-3) M) and gabaculine (10(-5) M), enhanced the stimulus-evoked release of GABA and reduced that of beta-alanine, while no change was observed in the release of glutamate. These changes in amino acid release from the slices were accompanied by an increase in the content of GABA and a decrease in that of beta-alanine. The stimulus-evoked release of these amino acids was abolished by Ca2+-deprivation, in either the presence or absence of GABA-T inhibitors. These results suggest a modulatory role of GABA-T for synaptically releasable GABA and involvement of this enzyme in the synthesis of releasable beta-alanine.

4-Aminobutyrate Transaminase↗
PubMed1988

Adrenaline as an endogenous agonist for presynaptic beta-adrenoceptors and their relevance to the development of hypertension in spontaneously hypertensive rats.

We attempted to identify an endogenous agonist for presynaptic facilitatory beta-adrenoceptors. Pulmonary arteries isolated from guinea pigs 5 days after bilateral adrenalectomy and renal arteries from 4-week-old spontaneously hypertensive rats (SHR) exposed to swimming stress for 1 h were preloaded with 3H-noradrenaline and superfused with Krebs medium. Electrical field stimulation was carried out four times at 15-min intervals (S1 to S4). Beta-antagonist carteolol at 10(-8), 10(-7) and 10(-6) mol/l was cumulatively applied after S1, S2 and S3 and the effect was estimated as the evoked 3H release ratio, Sx:S1. Catecholamine contents in arteries were measured by high performance liquid chromatography with electron capture. In sham-operated pulmonary arteries, carteolol inhibited evoked 3H release in a concentration-dependent manner. This inhibition was completely abolished by adrenalectomy. Adrenalectomy depleted adrenaline contents without modification of noradrenaline and dopamine. In renal arteries, swimming stress potentiated carteolol-induced concentration-dependent inhibition of evoked 3H release and increased adrenaline and dopamine contents without modification of noradrenaline. Adrenaline derived from adrenals and probably stored and coreleased with noradrenaline acts as an endogenous agonist for presynaptic beta-adrenoceptors.

Animals↗
PubMed1988

Transmitter-like release of endogenous 3,4-dihydroxyphenylalanine from rat striatal slices.

Biphasic electrical field stimulation (0.5-5 Hz, 2 ms, 25 V, 3 min) and high K+ (10-30 mM, 5 min) released endogenous 3,4-dihydroxyphenylalanine (DOPA) from superfused rat striatal slices. Characteristics of the DOPA release were compared with those of 3,4-dihydroxyphenylethylamine (dopamine, DA). Electrical stimulation at 2 Hz evoked DOPA and DA over similar time courses. alpha-Methyl-p-tyrosine (0.2 mM) markedly reduced release of DOPA but not of DA. Maximal release (0.3 pmol) of DOPA was obtained at 2 Hz and at 15 mM K+. The impulse-evoked release of DOPA and DA was completely tetrodotoxin (0.3 microM) sensitive and Ca2+ dependent and the 15 mM K+-evoked release was also Ca2+ dependent. On L-[3,5-3H]tyrosine (1 microM) superfusion, high K+ (15 and 60 mM) released DOPA and DA together with concentration-dependent decreases in tyrosine 3-monooxygenase (EC 1.14.16.2) activity as indicated by [3H]H2O formation, followed by concentration-dependent increases after DOPA and DA release ended. These findings suggest that striatal DOPA is released by a Ca2+-dependent excitation-secretion coupling process similar to that involved in transmitter release.

Animals↗
PubMed1988

Regional changes in brain noradrenergic activity elicited by a decrease in blood pressure.

Using high performance liquid chromatography with electrochemical detection, the level of 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), an index of noradrenaline release, was determined in regions of the brainstem and hypothalamus of rats after acute hypotension induced by hydralazine. In hypotensive rats, an increase in MHPG concentrations was observed in the posterior hypothalamus, while no significant changes were seen for all the other regions. These results suggest that hypotension results in an enhancement of noradrenaline release in the posterior hypothalamus in rats.

Animals↗
PubMed1988

Effects of prostaglandins E1, E2, F2 alpha and I2 on adrenergic transmission in guinea pig pulmonary arteries.

Effects of some prostaglandins (PGs) on adrenergic transmission were studied in guinea pig pulmonary arteries preloaded with 3H-norepinephrine. PGE1 and PGE2 at 0.1 to 100 nM concentration-dependently inhibited 3H-release and contraction evoked at 5 Hz. This inhibition was antagonized by diphloretin phosphate. PGF2 alpha at 1 to 100 nM had no effect on evoked 3H-release and contraction. PGI2 at 1 to 100 nM also failed to modify evoked 3H-release, but markedly and concentration-dependently decreased evoked contraction. There exist presynaptic inhibitory PGE1 and PGE2 receptive sites on adrenergic neurons innervating guinea pig pulmonary arteries, whereas PGF2 alpha and PGI2 produced no effect on the adrenergic neurons.

Adrenergic Fibers↗
PubMed1988

[A case of intrahepatic bile duct cancer responding to 5-fluorouracil, adriamycin and mitomycin C chemotherapy].

A 64-year-old woman who was diagnosed as inoperable intrahepatic bile duct cancer with massive liver metastasis was treated with 5-fluorouracil (5-FU), adriamycin (ADM) and mitomycin-C (MMC). Obstructive jaundice was reduced and performance status was soon improved by this regimen. The reduction rate of the tumor was noted to be more than 50% on CT images, so this patient was considered to have achieved a partial response. In histological examination, well differentiated tubular adenocarcinoma cells were degenerated and replaced fibrous tissue. Thus, it was considered that the reduction of the tumor was caused by these phenomena. This case suggested the activity of 5-FU, ADM and MMC combination for bile duct cancer.

Adenocarcinoma↗
PubMed1987

Cardiovascular effects in rats of alpha 1 and alpha 2 adrenergic agents injected into the nucleus tractus solitarii.

The cardiovascular effects of selective alpha 1 and alpha 2 agonists and antagonists injected into the nucleus tractus solitarii (NTS) were studied in urethane-anesthetized rats. Methoxamine (0.3-3 micrograms) injected bilaterally into the NTS caused a dose-dependent increase in blood pressure and heart rate. Phenylephrine (6 micrograms) and an imidazolidine derivative St 587 (3 micrograms) similarly injected also produced an increase in blood pressure, whereas alpha-methylnoradrenaline and an azepine derivative B-HT 920 (1 and 3 micrograms) caused a decrease in blood pressure and heart rate. The pressor response to methoxamine (1 microgram) was markedly inhibited by prazosin (0.3 microgram) injected into the same sites or hexamethionum (25 mg/kg, i.v.). Prazosin (0.3 microgram) alone injected bilaterally into the NTS did not affect the blood pressure, while yohimbine (0.1 microgram) similarly injected increased the pressure. These results suggest that in the rat NTS there exist alpha 1 adrenoceptors responsible for an increase in arterial pressure. The NTS alpha 2 adrenoceptors seem to be involved in the tonic regulation of arterial pressure.

Adrenergic alpha-Agonists↗
PubMed1987

Presynaptic angiotensin II receptors and captopril-induced adrenergic transmission failure probably not via converting enzyme inhibition in guinea-pig pulmonary arteries.

This study aimed to clarify whether or not captopril modifies the activity of an intrinsic, presynaptic, angiotensin II receptor system within the vasculature in superfused spiral preparations of guinea-pig pulmonary arteries preloaded with 3H-norepinephrine. Angiotensins I and II dose-dependently facilitated 3H efflux and contraction evoked by transmural field stimulation at 5 Hz. A conversion rate of angiotensin I to angiotensin II calculated from the dose-response curves was 26.7 +/- 2.6%. 1Sar-8Ile-angiotensin II alone did not decrease the evoked 3H efflux and contraction, but antagonized the facilitation induced by angiotensins I and II. Captopril (1 and 10 mumol) inhibited the facilitation by angiotensin I but produced no effect on that by angiotensin II. Captopril alone at 1 mumol attenuated the evoked 3H efflux and contraction without decreasing contractile responses to exogenously applied norepinephrine, but the higher concentrations produced no further dose-dependent attenuation. Indomethacin alone produced no increases in the evoked 3H efflux. Captopril at 1 mumol still attenuated the evoked 3H efflux in the presence of indomethacin. On the other hand, enalaprilat alone (0.1-100 mumol) produced no effect on the evoked 3H efflux and contraction. Thus, in guinea-pig pulmonary arteries, angiotensin I is intramurally converted to angiotensin II, and there are presynaptic angiotensin II receptors to facilitate norepinephrine release. However, captopril-induced presynaptic adrenergic transmission failure appears to be dependent neither on an intrinsic angiotensin system nor on a prostaglandin-related mechanism.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1987

Potassium induced release of endogenous glutamate, gamma-aminobutyric acid (GABA) and glycine from the caudal dorsomedial medulla of the rat.

Release of endogenous glutamate, gamma-aminobutyric acid (GABA) and glycine was investigated in the caudal dorsomedial (CDM) region of the rat medulla oblongata. High potassium stimulation (50 mM) produced an increase in release of glutamate, GABA and glycine by 579.1, 303.4 and 774.5 (pmol/mg protein), respectively. The release was abolished by Ca2+ deprivation. These results indicate a possible neurotransmitter role for glutamate, GABA and glycine in the CDM medulla of the rat.

Animals↗
PubMed1987

A trial for kinetic evaluation of the antagonistic potency of several beta-antagonists on presynaptic beta-adrenoceptors.

The antagonistic potency, pA2, of several non-selective beta-antagonists on presynaptic beta-adrenoceptors was evaluated using a parallel line assay and MacKay's equation against isoproterenol-induced increases in 3H release in isolated guinea-pig pulmonary arteries preloaded with 3H-norepinephrine. Cumulatively applied isoproterenol at 10(-9) M, 10(-8) M and 10(-7) M dose-dependently increased 3H release evoked by transmural field stimulation at 1 Hz. beta-Antagonists tested dose-dependently antagonized the isoproterenol-induced increases. The order of pA2 was carteolol (11.23 +/- 0.09) greater than nadolol (9.78 +/- 0.05) greater than pindolol (9.59 +/- 0.03) greater than propranolol (9.26 +/- 0.17). Carteolol has the highest pA2 and is a useful tool for clarifying whether or not presynaptic beta-adrenoceptors tonically function.

Adrenergic beta-Antagonists↗
PubMed1987

Some relevance of presynaptic beta-adrenoceptors to development of hypertension in spontaneously hypertensive rats.

The effect of cumulatively applied carteolol alone 10(-8) M to 10(-6) M on [3H] release evoked by transmural field stimulation at 5 Hz was studied in renal and mesenteric arteries preloaded with [3H]-norepinephrine, from prehypertensive 4 weeks old and hypertensive 14 weeks old spontaneously hypertensive rats (SHR) and age-matched Wistar Kyoto rats (WKY). The [3H] release in renal and mesenteric arteries from young SHR was greater than that from age-matched WKY, whereas there was no difference of the parameter in both arteries from adult rats of both strains. In renal arteries, carteolol 10(-6) M inhibited [3H] release in young SHR and the inhibition differed from no effect in age-matched WKY, but the inhibition was not seen in adult SHR and WKY. In mesenteric arteries, carteolol 10(-7) M and 10(-6) M concentration-dependently inhibited [3H] release in young SHR and WKY, the antagonist 10(-6) M inhibited the parameter in adult SHR and WKY and the inhibition in young SHR was greater than that in age-matched WKY, whereas the inhibition in adult SHR was smaller than that in age-matched WKY. Presynaptic beta-adrenoceptors may function tonically to facilitate the release of norepinephrine in renal arteries from young SHR and in mesenteric arteries from young and adult SHR and WKY. The modifications of these adrenoceptors in young SHR appear to have causal relevance to development of the hypertension.

Animals↗
PubMed1987

Pharmacological characterization of spinal alpha adrenoceptors related to blood pressure control in rats.

The effects of various alpha adrenoceptor agonists and antagonists injected into the spinal subarachnoid space on blood pressure and heart rate were investigated in pentobarbital-anesthetized male rats. A dose-dependent decrease in blood pressure and heart rate was induced by intrathecal injections of clonidine (0.3-3 micrograms), at the T6-T7 level. Guanabenz (3-30 micrograms) and an azepine derivative B-HT 920 (1-3 micrograms) also reduced blood pressure and heart rate. In contrast, an imidazolidine derivative St 587 (10 micrograms) was ineffective. The clonidine-induced hypotensive effect was antagonized by yohimbine but not by prazosin. Yohimbine (3-10 micrograms) alone caused an increase in blood pressure and heart rate while only a weak hypotenion occurred with prazosin (10 micrograms). Pretreatment with intrathecal 6-hydroxydopamine (50 micrograms X 2) did not impair the hypotensive action of clonidine (1 microgram) whereas the hypertensive effect of yohimbine was reduced markedly by this treatment. When injected i.v. or intrathecally at the C1-C2 level, clonidine (1 microgram) produced only a slight decrease in blood pressure. It is concluded that, in rat spinal cord, alpha-2 adrenoceptors located postsynaptically are involved in blood pressure control. Endogenous catecholamines, especially norepinephrine in the spinal cord seem to activate tonically the alpha-2 adrenoceptors.

Adrenergic alpha-Antagonists↗
PubMed1986

Biphasic actions of L-DOPA on the release of endogenous dopamine via presynaptic receptors in rat striatal slices.

In rat striatal slices, 30 nM of L-DOPA increased the impulse (5 Hz)-evoked release of dopamine (DA), without increasing the spontaneous release and tissue content of DA. The minimum dose required to increase spontaneous DA release was 0.1 microM and the dose which led to an accumulation of DA was 100 microM. In the presence of NSD-1055, a DOPA-decarboxylase inhibitor, L-DOPA-induced increases in spontaneous DA release were prevented and L-DOPA produced dual actions on the evoked release of DA, a stereoselective propranolol-sensitive increase at 30 nM and a stereoselective sulpiride-sensitive decrease at 1 microM. L-DOPA produces dual presynaptic regulatory actions on DA release, via facilitatory beta-adrenoceptors at 30 nM and inhibitory DA receptors at 1 microM. The primary action of L-DOPA appears to be the facilitation of release of DA rather than the conversion to DA.

Animals↗
PubMed1986

Diminished alpha 2-adrenoceptor-mediated modulation of noradrenergic neurotransmission in the posterior hypothalamus of spontaneously hypertensive rats.

An azepine derivative, 6-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo-[4,5-d]-azepine (B-HT 920; 100 nM), inhibited the evoked noradrenaline release from slices of rat posterior hypothalamus, and yohimbine (100 nM) potentiated the release from slices of rat anterior and posterior hypothalamus. In the posterior hypothalamus of 4- and 15-16-week-old spontaneously hypertensive rats (SHRs), as compared with age-matched Wistar-Kyoto rats (WKYs), the inhibitory effect of B-HT 920 and the facilitatory effect of yohimbine were decreased. In the anterior hypothalamus there was no significant difference in the yohimbine effect between WKYs and SHRs, at either age. It is concluded that alpha 2-adrenoceptor-mediated autoinhibition of noradrenergic neurotransmission is diminished in the posterior hypothalamus of SHRs.

Animals↗
PubMed1986

Biphasic actions of L-DOPA on the release of endogenous noradrenaline and dopamine from rat hypothalamic slices.

Effects of L-DOPA on the release of endogenous noradrenaline and dopamine from rat hypothalamic slices evoked by electrical field stimulation at 5 Hz were investigated in the absence and presence of p-bromobenzyloxyamine (NSD-1055), a DOPA-decarboxylase inhibitor. In the absence of NSD-1055, L-DOPA produced a facilitation of impulse-evoked release of noradrenaline at 0.1 microM but not at 1 and 10 microM, and had no effect on the spontaneous release. On the other hand, L-DOPA 0.1 to 10 microM dose-dependently increased the spontaneous release of dopamine and the highest concentration only increased the evoked release and tissue content of dopamine. In the presence of NSD-1055 10 microM, the increase in the spontaneous release of dopamine was prevented and L-DOPA produced biphasic regulatory effects on the evoked release of noradrenaline and dopamine, a facilitation at 0.1 microM and an inhibition at 1 microM. The facilitation was antagonized by (-)-propranolol 0.1 microM, but not by the (+)-isomer, whereas the inhibition was antagonized by S-sulpiride 1 nM, but not by the R-isomer. In conclusion, L-DOPA appears to produce biphasic actions on the release of endogenous noradrenaline and dopamine from rat hypothalamic slices, not through its conversion to dopamine but through presynaptic regulatory mechanisms, an inhibition via dopamine receptors at a micromolar concentration and a facilitation via beta-adrenoceptors at the lower concentration.

Animals↗
PubMed1986

Evidence for the existence of stereoselective presynaptic beta 1-adrenoceptors on noradrenergic and dopaminergic neurons in the rat hypothalamus.

Using high performance liquid chromatography with an electrochemical detector, we examined antagonistic effects of l- and d-acebutolol and atenolol against isoproterenol-induced facilitation of impulse-evoked release of endogenous norepinephrine and dopamine in rat hypothalamic slices. Isoproterenol (10 nM) increased the release of the both catecholamines, and this facilitation was similarly antagonized by 100 nM l-acebutolol and 100 nM atenolol, but was not antagonized by 100 nM d-acebutolol. In conclusion, there exist stereoselective presynaptic beta 1-adrenoceptors on noradrenergic and dopaminergic neurons in the rat hypothalamus.

Animals↗
PubMed1986

Cardiovascular effects of L-glutamate and gamma-aminobutyric acid injected into the rostral ventrolateral medulla in normotensive and spontaneously hypertensive rats.

We studied the responses to chemical stimulation of the ventrolateral medulla in pentobarbital-anaesthetized, paralyzed, normotensive and spontaneously hypertensive (SHR) rats. When unilaterally injected into a circumscribed region of the rostral ventrolateral medulla, L-glutamate (0.16-1.6 nmol) elicited a dose-dependent increase in arterial pressure and heart rate. Bilateral microinjections of L-glutamate diethylester (63 nmol), an antagonist of excitatory amino acids, into the glutamate-sensitive sites markedly reduced arterial pressure and heart rate. gamma-Aminobutyric acid (GABA) (0.3-3 nmol) injected into the glutamate-sensitive sites caused a dose-dependent decrease in arterial pressure and heart rate. The depressor response to GABA was smaller in SHR than that in normotensive Wistar Kyoto rats (WKY), while there were no differences between WKY and SHR in the pressor response to L-glutamate. Thus, a depressor function involving the ventrolateral medulla appears to be diminished in SHR.

Animals↗