Biomedical subjects

Y Kasuya

Publications and source records attributed to Y Kasuya.

At least 217 records · Page 12Linked to original sources

PubMed1991

The abilities of specific kappa-opioid agonists, U-50,488H and U-62,066E, to cause antitussive tolerance were lower than that of morphine.

We examined whether the chronic administration of selective kappa-opioid agonists could produce antitussive tolerance, in a comparison with the mu-opioid morphine. A certain degree of tolerance to the antitussive effects of morphine appeared in rats treated chronically with this drug. However, chronic administration of U-50,488H and U-62,066E, highly selective agonists for the kappa-opioid receptor, does not result in the development of tolerance to their respective antitussive effects. These results suggest that the ability of kappa-opioid agonists to cause tolerance to their respective antitussive effects was lower than that of a mu-opioid agonist.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1991

NZ-105, a new 1,4-dihydropyridine derivative: correlation between dihydropyridine receptor binding and inhibition of calcium uptake in rabbit aorta.

The correlation between the binding of NZ-105, a newly synthesized 1,4-dihydropyridine (DHP) derivative, on DHP receptors and its inhibitory activity on transmembrane 45Ca2+ uptake was investigated. 3H-NZ-105 bound rabbit aortic microsomes more slowly than did 3H-nitrendipine (3H-NTD): the association and dissociation rate constants of 3H-NZ-105 were about 70 times and 10 times less than those of 3H-NTD, respectively. The dissociation constant (Kd) of 3H-NZ-105 (4.48 nM) was about 6 times larger than that of 3H-NTD (0.79 nM), and the maximum number of binding sites (Bmax) for 3H-NZ-105 (112.5 fmoles/mg protein) was about the same as that for 3H-NTD (106.2 fmoles/mg protein). Unlabelled NZ-105 and nicardipine fully, and in a concentration-dependent manner, displaced 3H-NZ-105 specific binding. Pre-incubation with NZ-105 also concentration-dependently (more than 0.1 microM) inhibited the transmembrane 45Ca2+ uptake increment induced by a high-K+ (50 mM) solution. The inhibitory efficacy of NZ-105 became larger as the incubation period with this compound increased (from 1 hr incubation to 3 hr incubation), and recovery was difficult even after washout for 3 hr. Based on these results, we conclude that NZ-105 causes blockade of voltage-dependent calcium channels (VDCs) by binding to DHP receptors. Moreover, the very slow onset and recovery from NZ-105-induced vasodilation may be attributable to the slow and long-lasting inhibition of transmembrane calcium uptake, which accompanies its very slow binding to and dissociation from DHP receptors.

Animals↗

PubMed1991

Endothelin-1-induced phosphorylation of the 20-kDa myosin light chain and caldesmon in porcine coronary artery smooth muscle.

Endothelin-1 (ET), a potent vasoconstrictor, induces a sustained increase in the phosphorylation level of the 20-kDa myosin light chain (MLC) in porcine coronary artery strips. ET also induces late phosphorylation of caldesmon, which is mimicked by 12-deoxyphorbol 13-isobutyrate, but not by 60 mM KCl. Nitroglycerin, a vasorelaxant, completely reverses the ET-induced phosphorylation of MLC, but not that of caldesmon. These results suggest an important regulatory role of MLC phosphorylation in ET-induced contraction.

Animals↗

PubMed1991

Pharmacological actions of chemically-modified phospholipase A2 from the venom of Trimeresurus flavoviridis on the smooth muscle of the rat stomach fundus.

The pharmacological activities of Trimeresurus flavoviridis phospholipase A2 (PLA2) and their chemically-modified PLA2 were characterized by measuring the contraction of rat stomach fundus strips. The native PLA2 produced a contraction of rat fundus strips. The alpha-amino-modified enzyme induced an almost identical contraction of the fundus with that of the native enzyme, whereas His-modified and Lys-modified enzymes induced a markedly decreased contraction as compared with the native enzyme. These results demonstrate that lysine and histidine residues but not the alpha-amino group in the PLA2 molecule are essential for contractile activity of the stomach fundus.

Animals↗

PubMed1991

Effects of chronic diabetes on vascular responses of basilar artery and aorta from rabbits with alloxan-induced diabetes.

The influences of chronically diabetic states on contraction and relaxation responses of the isolated basilar artery and aorta to various vasoactive agents were examined in alloxan-induced diabetic rabbits with 2 years duration. There were no significant differences in the reactivities of basilar artery to norepinephrine (NE), 5-hydroxytryptamine (5-HT) and KCl between age-matched control and diabetic rabbits. Maximal contractions of aorta with endothelium in response to NE and 5-HT were significantly enhanced in case concentration-response curves for NE and 5-HT-induced contractions in the aorta without endothelium from diabetic rabbits were not different from those from age-matched control rabbits. Acetylcholine-induced relaxations in both the basilar artery and aorta from diabetic rabbits were significantly attenuated compared with those from age-matched control rabbits. However, no differences were observed in concentration-response curves for sodiumnitroprusside-induced relaxations in both the basilar artery and aorta between diabetic rabbits and age-matched control rabbits. These results indicate that chronic diabetes induces an specific enhancement in the contractile responses to NE and 5-HT in aorta and an attenuation in the endothelium-dependent relaxation in both the basilar artery and aorta. These results further demonstrated that the cerebral artery is resistant to diabetes of 2 years duration as compared with the peripheral artery.

Acetylcholine↗

PubMed1991

Modulation by serotonin of glutamate-induced lethality in mice.

To determine the involvement of serotonergic mechanisms in glutamate-induced excitotoxicity, the effects on glutamate-induced lethality of drugs that modify serotonergic transmission were studied in mice. Monosodium glutamate (MSG; 6-10 g/kg, i.p.) produced a dose-related increase in lethality in mice. Pretreatment with reserpine (2.5 mg/kg, i.p., 5 hr) resulted in an increase in MSG-induced lethality. p-Chlorophenylalanine (PCPA; 300 mg/kg, i.p. 24 hr) specifically produced a reduction of more than 60% in the level of 5-HT in the brain. PCPA-treated mice were also more sensitive to the lethal effects of MSG. alpha-Methyl-p-tyrosine (300 mg/kg, i.p. 5 hr) produced a significant reduction in the levels of norepinephrine and dopamine in the brain, but the sensitivity to the lethal effects of MSG was unchanged. L-Tryptophan (300 and 500 mg/kg, i.p.) and 5-hydroxy-L-tryptophan (5-HTP; 3-30 mg/kg, i.p.), precursors of serotonin (5-HT), protected mice to a significant extent against MSG-induced lethality, in a dose-related manner. 1-(m-Trifluoromethylphenyl) piperazine (TFMPP; 50 mg/kg, i.p.), an agonist of 5-HT1 receptor, was also associated with protection against MSG-induced lethality. This protective effect was not observed in PCPA- or methysergide-treated mice. These results suggested that 5-HT in the brain may play an inhibitory role in MSG-induced excitotoxicity.

5-Hydroxytryptophan↗

PubMed1991

Effects of CD-349, a dihydropyridine derivative, on contraction induced by vasoactive agents in canine basilar artery after subarachnoid hemorrhage.

We investigated the effects of CD-349, a dihydropyridine derivative, on contraction induced by vasoactive agents in canine basilar artery after subarachnoid hemorrhage (SAH). Ca(2+)-induced contraction of basilar arterial strips preincubated with serotonin (5-HT, 3x10(-6)M) was potentiated in strips from SAH. However, Ca(2+)-induced contraction of arterial strips which were depolarized with isotonic K+ (64mM) was attenuated in strips from SAH. These Ca(2+)-induced contractions of the basilar arteries preincubated with 5-HT and K+ from both control and SAH dogs were significantly inhibited by CD-349 and nicardipine, both dihydropyridine derivatives. 5-HT contracted the basilar arterial strips in a concentration-dependent manner; however, the maximal contraction of the basilar arterial strips to 5-HT was enhanced in SAH. Endothelium-dependent relaxation in response to substance-P was attenuated in SAH when compared to that in control dogs. Early treatment with CD-349 (1 or 2mg/kg/day, i.m.) for 1 week reversed not only the enhanced contraction of the basilar artery in response to 5-HT but also the impairment of endothelium-dependent relaxation in response to substance-P in SAH. It is expected that CD-349 may be a useful agent for the treatment of cerebrovascular diseases such as SAH.

Animals↗

PubMed1990

Antitussive effects of two specific kappa-opioid agonists, U-50,488H and U-62,066E, in rats.

The effects of highly selective agonists of kappa-opioid receptors, namely U-50,488H and U-62,066E, on the capsaicin-induced cough reflex in rats were studied. Intracisternal (i.cist.) injection of U-50,488H and of U-62,066E significantly decreased the number of coughs in a dose-dependent manner. The antitussive potency of i.cist. injection of these two kappa-opioid agonists was similar to that of morphine. Intraperitoneal (i.p.) injection of U-50,488H and of U-62,066E also decreased the number of coughs, again in a dose-dependent manner. The antitussive effects of U-50,488H and U-62,066E were blocked by norbinaltorphimine, an antagonist of kappa-opioid receptors. Methysergide, administered i.cist. (3 nmol), antagonized the antitussive effects of U-50,488H and U-62,066E. However, ketanserin had no effect on the antitussive effects of these kappa-opioid agonists. These data suggest that U-50,488H and U-62,066E exert their antitussive effect on rats through stimulation of kappa-opioid receptors. Furthermore, with respect to the antitussive effects of kappa-opioid agonists, the system that involves 5-HT1 receptors may be more important than the system that involves 5-HT2 receptors.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1990

[Experimental study relating to the anti-cancer effect of doxifluridine].

UNLABELLED: We investigated the anti-cancer effect of Doxifluridine (5'-deoxy-5-fluorouridine: 5'-DFUR) on an experimentally prepared tumor bearing mouse. METHOD: A 20-methylcholanthrene induced squamous cell cancer was prepared on the skin of ddN female mouse and 5'-DFUR was administered orally by catheter (90 mg/kg, 150 mg/kg, 210 mg/kg and physiological saline 0.5 ml/body). The each group consisted of 10 mice. Oral medications were performed once a day for one week (6 days continuous duration) and these medications were continued during a total period of four weeks. Once a week, the general condition of the animals was checked and at the same time, the size (length x width) of the tumor was measured, and the anti-cancer effect was determined. RESULT: It was noted between the control and 5'-DFUR medication group that there was a marked effectiveness on the rate of decrease in size and disappear of the squamous cell cancer according to the medication of 5'-DFUR. It regarded to the amount of 5'-DFUR, that there was a significant difference in the anti-cancer effect between 90 mg/kg and 210 mg/kg groups and between 150 mg/kg or 210 mg/kg and control groups. However, the difference could not be observed between 90 mg/kg and 150 mg/kg groups and between 150 mg/kg and 210 mg/kg groups.

Administration, Oral↗

PubMed1990

Simultaneous measurements of endogenous and deuterium-labelled tracer variants of androstenedione and testosterone by capillary gas chromatography-mass spectrometry.

A capillary gas chromatographic-mass spectrometric method for the simultaneous determination of androstenedione and testosterone in human plasma using [19,19,19-2H3]androstenedione and [19,19,19-2H3]testosterone as internal standards is described. For calculation of plasma androstenedione and testosterone, peak heights were measured by selected-ion monitoring of the molecular ions of the heptafluorobutyryl derivatives of androstenedione and [2H3]androstenedione (m/z 482 and 485) and of testosterone and [2H3]testosterone (m/z 680 and 683). The isotope dilution method needed no complex corrections for contributions and provides a sensitive and reliable technique with good accuracy, precision and reproducibility.

Androstenedione↗

PubMed1990

Diurnal rhythm in the plasma concentration of cortisol in paediatric patients with orthostatic dysregulation.

A gas chromatographic/mass spectrometric method using stable isotopically labelled cortisol as an internal standard was employed to determine patterns of episodic secretion of cortisol in three normal subjects and four paediatric patients with orthostatic dysregulation. The measurement of the plasma cortisol level at frequent time intervals revealed how the daily secretory pattern of cortisol differs in these patients and normal subjects.

Adolescent↗

PubMed1990

Development of supersensitivity to substance P in the spinal cord of the streptozotocin-induced diabetic rats.

To investigate the possible mechanisms involved in the alterations in sensitivity to pain in diabetic rats, we examined the influence of diabetes induced by streptozotocin (STZ) on the functions of the neuronal systems that contain substance P (SP) within the spinal cord. The threshold for pain perception as determined by a tail-pinch test was significantly reduced in diabetic rats. The levels of SP in the spinal cord from diabetic rats (116.9 +/- 16.3 pmol/g tissue) were significantly lower than those from the control rats (190.2 +/- 14.1 pmol/g tissue). Diabetic rats were found to have a significant increase in the number of binding sites for SP in dorsal spinal cord. The concentrations of binding sites in diabetic rats and in control rats were 102.1 +/- 17.3 fmol/mg protein and 52.6 +/- 6.6 fmol/mg protein, respectively. These data indicate that STZ-induced diabetic rats exhibit supersensitivity to SP in the spinal cord. This may be correlated, in part, with the reduction in the threshold for perception of pain in diabetic animals.

Animals↗

PubMed1990

Effects of endothelin on the portal vein from spontaneously hypertensive and Wistar Kyoto rats.

The effects of endothelin, a novel potent vasoconstrictor peptide, on isolated portal veins were examined in spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). Endothelin contarcted the portal vein from SHR and WKY, in a concentration-dependent manner. However, both twitch contraction and tonic contraction of portal veins in response to endothelin were significantly enhanced in SHR. In contrast to the effects of endothelin, twitch contractile responses to Bay K 8644 were not significantly different between vessels from SHR and WKY. These results indicate that endothelin is a potent vasoconstrictor peptide in the portal vein, and that the increased sensitivity in SHR may be due to an increase in the activity of voltage-dependent Ca2+ channels which is modulated by endothelin, but not to an increase in the activity of voltage-dependent Ca2+ channels which can be stimulated by Bay K 8644.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1990

Differences in vascular responses to vasoactive agents of basilar artery and aorta from rabbits with alloxan-induced diabetes.

Responses of the basilar artery and aorta to vasoactive agents in alloxan-induced diabetic and age-matched control rabbits were examined. There were no significant differences in the reactivity of the basilar artery to norepinephrine (NE), 5-hydroxytryptamine (5-HT), and K+ between age-matched control and diabetic rabbits. The maximal contraction of the aorta with endothelium in response to NE was significantly enhanced in the case of the aorta from diabetic rabbits. Pretreatment with 10(-6) M methylene blue or removal of the endothelium enhanced the contractile response of aorta to NE from control rabbits and, after such treatment, the concentration-response curve to NE was almost identical to that of aorta from diabetic rabbits. Basal levels of cyclic GMP but not cyclic AMP in the diabetic aorta with endothelium were significantly lower than those in the control aorta with endothelium. These results demonstrate that the cerebral artery is resistant to diabetes mellitus within 10 weeks as compared with the peripheral artery. The enhancement in the contractile response of aorta to NE in diabetic rabbits is due to the attenuation of the spontaneous release of endothelium-derived relaxing factor, through an impairment of the function of endothelial cells.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1990

Endothelin receptor is coupled to phospholipase C via a pertussis toxin-insensitive guanine nucleotide-binding regulatory protein in vascular smooth muscle cells.

The mechanisms of endothelin-1 (ET) actions were investigated in cultured rat aortic vascular smooth muscle A-10 cells. The A-10 cells have a single class of high affinity binding sites for ET with an apparent Mr of 65,000-75,000 on SDS-PAGE. Stimulation of cells with ET induces mobilization of Ca2+ from both intra- and extracellular pools to produce a biphasic increase in cytoplasmic free Ca2+ concentration. ET increases cellular levels of inositol trisphosphate and 1,2-diacylglycerol, indicating activation of phospholipase C by ET. ET stimulates production of inositol phosphates in membranes prepared from A-10 cells in the presence of guanosine 5'-O-(thiotriphosphate) (GTP gamma S), but not in its absence. Further, specific binding of 125I-labeled ET to A-10 cell membranes is shown to be inhibited by GTP gamma S in a dose-dependent manner. Treatment of A-10 cells with pertussis toxin induces ADP-ribosylation of a 41,000-D membrane protein but fails to block the ET-induced increases in inositol phosphate production and Ca2+ mobilization. These results indicate that the receptor for ET is coupled to phospholipase C via a guanine nucleotide-binding regulatory protein which is distinct from the pertussis toxin substrate in A-10 cells.

Animals↗

PubMed1990

Propranolol blocks cocaine-induced potentiation of the contraction in the smooth muscle of the rat vas deferens.

In the smooth muscle of the rat vas deferens, 10(-5) M cocaine shifted the dose-response curve to norepinephrine to the left and enhanced the maximal contractions to norepinephrine and methacholine. Propranolol at 10(-4) M almost completely blocked these potentiating effects of cocaine. Sotalol or lidocaine at 10(-4) M did not block the potentiating action of cocaine. The cocaine-induced enhancement of the methacholine contraction and its blockade by propranolol was observed in the dibenamine-treated vas deferens. Propranolol also blocked the depolarization-induced enhancement of the methacholine contraction. Together with the previous study demonstrating the calcium-antagonist action for propranolol, these results suggest that propranolol blocks the cocaine-induced enhancement by inhibiting the calcium influx through the potential-dependent calcium channel in the rat vas deferens.

Animals↗

PubMed1990

Effects of L-tryptophan on the effects of antitussives.

The effects of L-tryptophan and the major constituents of cough medicines on the antitussive effect of dihydrocodeine were examined in a comparative study with anesthetized rats. The antitussive effect of dihydrocodeine was enhanced by simultaneous administration of noscapine or methylephedrine. In rats treated with noscapine and methylephedrine together, the effect of dihydrocodeine was more markedly enhanced. Furthermore L-tryptophan reduced by half the antitussive ED50 (AtD50) of dihydrocodeine. There was no difference between the AtD50 of dihydrocodeine when administered in combination with noscapine and methylephedrine and that of dihydrocodeine when combined with noscapine and L-tryptophan. The AtD50 of noscapine and dextromethorphan was also reduced by about half when what was administered with L-tryptophan. By contrast, the liability with respect to physical dependence on dihydrocodeine was not enhanced by the simultaneous administration of L-tryptophan. These results suggest that L-tryptophan can be considered to be a useful constituent of antitussive preparations.

Animals↗

PubMed1990

Involvement of alpha 2-adrenergic receptors in the vagal reflex-induced tracheal constriction.

The effects of clonidine on the vagal reflex-induced tracheal constriction have been investigated in anesthetized, paralyzed, and artificially ventilated mongrel dogs. The cervical trachea was transected in situ into two parts. Responses of the tracheal musculature were measured as changes in the intratracheal pressure on an air-filled balloon introduced into the rostral side of the transected trachea. Reflex tracheal constriction was induced by afferent electrical stimulation at the central cut end of the vagus nerve. Drugs were injected or infused close intraarterially (i.a.) into the bilateral cranial thyroid arteries in such a way that each drug was applied just to the rostral trachea. The reflex tracheal constriction was abolished by a close i.a. infusion of 3 microM atropine. The magnitude of the reflex tracheal constriction was slightly reduced by a close i.a. infusion of 10 microM clonidine and was significantly reduced by the infusion of clonidine at a concentration of 100 and 300 microM. The response to 100 microM clonidine was antagonized by a close i.a. infusion of 1 microM yohimbine. The tracheal constriction induced by i.a. injection of 5.5 nmol acetylcholine was unaffected by infusion of 10, 100 and 300 microM clonidine. The vagal reflex-induced tracheal constriction seems to be inhibited by stimulation of prejunctional alpha 2-adrenoceptors.

Acetylcholine↗