Search PubMed⌕ Search

Biomedical subjects

Y Kasuya

Publications and source records attributed to Y Kasuya.

At least 91 records · Page 5Linked to original sources
PubMed1995

Effects of aminoglycoside antibiotics on cholinergic autonomic nervous transmission.

The effects of eight aminoglycoside antibiotics, gentamicin, neomycin B, ribostamycin, dibekacin B, kanamycin A, streptomycin, tobramycin and amikacin, and two non-aminoglycoside antibiotics, tetracycline and ampicillin, on cholinergic autonomic nervous transmission were studied using isolated guinea-pig ileum preparation. The aminoglycoside antibiotics blocked the transmurally elicited twitches of the ileum in a concentration-dependent manner. The blocking effect of aminoglycosides was biphasic, i.e., an initial reduction followed by a spontaneous partial recovery. Dibekacin was the most potent parasympathetic inhibitor, followed by neomycin B, tetracycline, gentamicin, streptomycin, kanamycin A, tobramycin, ribostamycin, and amikacin. Ampicillin had no blocking effect. The tested antibiotics did not affect acetylcholine (ACh)-induced contraction of the ileum, except for high concentrations of neomycin B, gentamicin, and streptomycin. The three antibiotics shifted the dose-response curves for ACh to the right without affecting the maximal contraction. Naloxon, yohimbine, hexamethonium and choline chloride failed to eliminate the blocking effect of the antibiotics on twitches of the ileum induced by transmural stimulation. However, increase of the extracellular Ca ion concentration virtually abolished the blockade. Dibekacin blocked the evoked but not the spontaneous release of ACh and shifted the dose-response curve of CaCl2-dependent transmurally elicited contractions of the ileum to the right. These results suggest that the site for the block of aminoglycosides is mainly the cholinergic nerve terminal, where they reduce the available Ca ions required for the release of ACh.

Acetylcholine↗
PubMed1995

Modification of mu-opioid agonist-induced locomotor activity and development of morphine dependence by diabetes.

We examined the locomotor-enhancing action of mu-opioid receptor agonists, such as morphine and [D-Ala2, N-MePhe4, Gly-ol5]enkephalin (DAMGO), and physical dependence on morphine in diabetic and nondiabetic mice. Morphine (5-20 mg/kg, s.c.) and DAMGO (1-4 nmol, i.c.v.) had a dose-dependent locomotor-enhancing effect in both nondiabetic and diabetic mice. The locomotor-enhancing effects of morphine and DAMGO were significantly less in diabetic mice than in nondiabetic mice, and were significantly reduced after pretreatment with either beta-funaltrexamine (20 mg/kg, s.c.), a selective mu-opioid receptor antagonist, or naloxonazine (35 mg/kg, s.c.), a selective mu1-opioid receptor antagonist. Both diabetic and nondiabetic mice were chronically treated with morphine (8-45 mg/kg, s.c.) for 5 days. During this treatment, neither diabetic nor nondiabetic mice showed any signs of toxicity. After morphine treatment, withdrawal was precipitated by injection of naloxone (0.3-10 mg/kg, s.c.). Several withdrawal signs, such as weight loss, diarrhea, ptosis, jumping and body shakes, were observed after naloxone challenge in morphine-dependent nondiabetic mice. Although morphine-dependent diabetic mice showed greater weight loss than nondiabetic mice, the incidence of jumping and body shakes after naloxone challenge in diabetic mice were lower than that in nondiabetic mice. These results suggest that diabetic mice are selectively hyporesponsive to mu1-opioid receptor-mediated locomotor enhancement. Furthermore, diabetes may affect mu1-opioid receptor-mediated naloxone-precipitated signs of withdrawal from physical dependence on morphine.

Animals↗
PubMed1995

Effect of diabetes on the morphine-induced inhibition of gastrointestinal transit.

The effect of diabetes on the morphine-induced inhibition of gastrointestinal transit was examined in mice. Morphine dose-dependently inhibited gastrointestinal transit after s.c. administration in both non-diabetic mice and diabetic mice. There was no significant difference between the ED50 values for this antitransit effect of morphine in non-diabetic and diabetic mice. The gastrointestinal antitransit effect of morphine was significantly antagonized by pretreatment with beta-funaltrexamine (40 mg/kg, s.c.), a selective mu-opioid receptor antagonist, in both non-diabetic and diabetic mice. However, pretreatment with naloxonazine (35 mg/kg, s.c.), a selective mu 1-opioid receptor antagonist, had no effect on the antitransit properties of morphine. These results suggest that diabetes failed to alter the mu 2-opioid receptor-mediated antitransit effect of morphine.

Animals↗
PubMed1995

Decreased Ca2+ influx into the endothelium contributes to the decrease in endothelium-dependent relaxation in the aorta of streptozotocin-induced diabetic mice.

Experiments were designed to investigate the role of Ca2+ influx into the endothelium in the relaxation of mouse aorta caused by acetylcholine (ACh) in streptozotocin (STZ)-induced diabetic and age-matched control mice. When Ca2+ was added to the bath, Ca2+ caused a transient contraction followed by relaxation in Ca(2+)-free medium containing 2 x 10(-6) M prostaglandin F2 alpha (PGF2 alpha) and 10(-5) M ACh in the control experiments. On the other hand, Ca2+ showed a long lasting contraction in STZ-induced diabetic rats. These results suggest that influx of Ca2+ into the endothelium is significantly attenuated in the diabetic vessels, and production or release of relaxing factor is markedly decreased.

Acetylcholine↗
PubMed1995

Endothelin-1-induced downregulation of ETB receptor mRNA: participation of cAMP.

In this study we examined the participation of cAMP formation in endothelin-1 (ET-1)-induced downregulation of ETB receptor mRNA in ROS 17/2 rat osteosarcoma cells. Dibutyryl cAMP induced downregulation of ETB receptor mRNA in a time-dependent manner. ET-1 induced production of inositol phosphates and an increase of cAMP level in ROS 17/2 cells. A stimulatory effect on cAMP level was also observed when A23187 plus PMA was added to the cells. The increase in cAMP level induced either by ET-1 or by A23187 plus PMA was inhibited by indomethacin. The downregulation of ETB receptor mRNA induced by ET-1 was significantly inhibited by indomethacin. These results suggest that the ET-1-induced downregulation of ETB receptor mRNA in ROS 17/2 cells may be partly mediated through the increase in cAMP level secondary to the activation of the phosphoinositide hydrolysis/Ca2+ transduction cascade.

Animals↗
PubMed1995

Increased endothelin-1 binding sites in the cardiac membranes in rats with chronic heart failure.

The effects of experimental chronic heart failure (CHF) on the density and affinity for endothelin-1 (ET-1) binding was studied in the rat heart. Because it has been reported that ET-1 binding sites on cultured cardiocytes are downregulated by pretreatment with ET-1, we also studied the plasma concentrations of ET-1 in rats with CHF. Three weeks after ligation of the left coronary artery, rats developed chronic heart failure (CHF rats). The plasma concentrations of ET-1, as measured by a sandwich-enzyme immunoassay, were significantly higher in CHF rats than in sham-operated rats [4.80 +/- 0.33 vs. 0.91 +/- 0.11 (mean +/- SEM) pg/ml; p < 0.01]. [125I]ET-1 binding experiments on rat cardiac membranes revealed that the binding site density (Bmax) was significantly higher in the CHF rats than in the sham-operated rats (243.0 +/- 20.0 vs. 154.8 +/- 17.4 fmol/mg protein; p < 0.05), whereas the values for the dissociation constant (Kd) were not different between the two groups (28.7 +/- 7.0 vs. 29.8 +/- 1.9 pM). Therefore, in the CHF rats, although plasma concentrations of ET-1 were elevated, the density of myocardial ET receptors was increased. Because ET-1 has potent inotropic and hypertrophic effects on cardiac myocytes, it is suggested that the effects of endogenous ET-1 in the heart are different between the CHF rats and the sham-operated rats.

Animals↗
PubMed1995

Altered production of endothelin-1 in the hypertrophied rat heart.

Although endothelin-1 (ET-1) has been shown to have potent hypertrophic effects in cultured cardiac myocytes, there is no evidence that the production of ET-1 is altered in the hypertrophied heart in vivo. We investigated mRNA and peptide levels of ET-1 in the rat heart hypertrophied due to pressure or volume overload. One week after surgery of abdominal aortic banding (AB) or aortic valve regurgitation (AR; the aortic valve was destroyed by a polyethylene catheter), the rats were sacrificed. Control sham-operated rats were also studied (AB-sham and AR-sham). The left ventricular (LV) weight to body weight ratio was significantly higher in AB rats than in AB-sham rats. It was also significantly higher in AR rats than in AR-sham rats. Therefore, AB rats and AR rats developed LV hypertrophy due to pressure and volume overload, respectively. The expression of ET-1 mRNA in the LV was markedly higher in AB rats than in AB-sham rats. The peptide level of ET-1 was also significantly higher in the LV of AB rats than in that of AB-sham rats. However, the expression of ET-1 mRNA in the LV of AR rats was similar to that of AR-sham rats. The present findings suggest that the production of ET-1 in the heart differs between pressure and volume overload-induced hypertrophy in rats.

Animals↗
PubMed1995

Possible sources of endothelin-1 in damaged rat brain.

We investigated the sources of endothelin-1 (ET-1) detected in the damaged brain tissue of rats after cold injury. ET-1 in the injured sites was increased 1-5 days after the injury. Physiologic observations revealed that breakdown of the blood-brain barrier occurred and that plasma-derived albumin exuded into the brain parenchyma after cold injury. Radiolabeled ET-1, which was injected into the left cardiac ventricle, was detected in the tissue at the injury site, and ET-1-like immunoreactivity was observed in the brain capillaries in the damaged tissues. TGF-beta 1, which is a tissue regeneration factor, potently induced the expression of ET-1 mRNA in cultured astrocytes. These results suggest that ET-1 is produced through a variety of ways in the damaged brain.

Animals↗
PubMed1995

Relationship between contractile responses and cytosolic free calcium levels in response to phorbol ester (PMA) in isolated rat aorta.

We examined the relationship between phorbol ester (PMA)-induced contractile response and cytosolic free calcium level in the rat aorta. PMA (10(-6)M) produced biphasic contraction, i.e., sustained contraction followed by a phasic response superimposed on the sustained contraction. Increase in [Ca2+]i was accompanied by a phasic but not sustained contraction. These results suggest that PMA-induced phasic contraction is dependent on Ca2+ influx but sustained contraction may be due to an increase in Ca2+ sensitivity of contractile protein.

Animals↗
PubMed1995

Pharmacokinetic studies of cortisol after oral administration of deuterium-labelled cortisol to a normal human subject.

A trace amount (5 mg) of stable isotopically labelled cortisol ([1,1,19,19,19-2H5]cortisol, cortisol-d5) was administered orally to a healthy human subject to examine the pharmacokinetic behaviour of exogenous cortisol and study the interconversion of cortisol to cortisone catalysed by 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD). The use of a gas chromatographic/mass spectrometric method allowed the simultaneous measurement of the plasma concentrations of endogenous and exogenous cortisol and cortisone. The amount administered was sufficiently small not to disturb or decrease the endogenous cortisol secretion by negative feedback. The appearance of cortisol-d5 and cortisone-d5 was very rapid. In a blood sample taken 10 min after administration of cortisol-d5, plasma concentrations of 154.8 ng ml-1 cortisol-d5 and 2.7 ng ml-1 cortisone-d5 were detected. A peak value of 196.6 ng ml-1 cortisol-d5 was observed 30 min after cortisol-d5 administration. The peak value of cortisone-d5 was 15.5 ng ml-1 40 min after cortisol-d5 administration, and thereafter cortisone-d5 declined in parallel with the slower decline phase of cortisol-d5. The plasma concentrations fell as low as 26.9 ng ml-1 for cortisol-d5 and 4.6 ng ml-1 for cortisone-d5 4 h after cortisol-d5 administration. The ratio of cortisone-d5 to cortisol-d5 approached a plateau 2 h after cortisol-d5 administration, reaching a constant value of approximately 0.15 thereafter. The higher value of the cortisone/cortisol concentration ratio (0.14-0.81; average 0.30) than the cortisone-d5/cortisol-d5 ratio may provide important information about the possibility that cortisone might be formed not only via the pathway of the cortisol conversion but also through other biotransformation processes.

Adrenal Cortex Hormones↗
PubMed1994

Endothelin-1 activates mitogen-activated protein kinases through two independent signalling pathways in rat astrocytes.

Northern blot analysis and displacement study revealed that the endothelin (ET) receptor functionally expressed in rat primary cultured astrocytes is the ETB receptor. Mitogen-activated protein kinases (MAP kinases) in the cells were activated by 10 nM ET-1, a dose that maximally stimulated phosphoinositide hydrolysis. This activation was potently inhibited by pretreatment of the cells with phorbol 12-myristate 13-acetate (PMA) which leads to protein kinase C (PKC) down-regulation and was slightly inhibited by pretreatment with pertussis toxin (PTX). Pretreatment of the cells with PMA plus PTX completely inhibited the ET-1-augmented MAP kinase activity. Activation of MAP kinases was also induced by 0.1 nM ET-1, which hardly stimulated phosphoinositide hydrolysis. This activation was fully inhibited by pretreatment with PTX but insensitive to pretreatment with PMA. ET-1-stimulated production of inositol phosphates was not affected by pretreatment with PTX. These results suggest that activation of MAP kinases secondary to stimulation of the ETB receptor with ET-1 in rat primary cultured astrocytes was mediated through two independent signalling pathways. PKC-dependent pathway and PTX-sensitive G protein-mediated pathway.

Animals↗
PubMed1994

Effects of diabetes on the morphine-induced Straub tail reaction in mice.

The effects of diabetes on the morphine-induced Straub tail reaction were examined in mice. The Straub tail reaction induced by s.c. administration of morphine was significantly less in diabetic mice than in non-diabetic mice. The morphine-induced Straub tail reaction was significantly reduced following pretreatment with beta-funaltrexamine, a selective mu-opioid receptor antagonist, in both diabetic and non-diabetic mice. Furthermore, the morphine-induced Straub tail reaction was also significantly reduced in both diabetic and non-diabetic mice following pretreatment with naloxonazine, a selective mu1-opioid receptor antagonist. These results suggest that mice with diabetes are hypo-responsive to mu1-opioid receptor-mediated Straub tail reaction.

Animals↗
PubMed1994

Effects of diabetes on spontaneous locomotor activity in mice.

Spontaneous locomotor activity in diabetic mice was significantly greater than that in non-diabetic mice. Haloperidol and SCH23390, a selective dopamine D1-receptor antagonist, significantly reduced spontaneous locomotor activity in diabetic mice, but not in non-diabetic mice. Spontaneous locomotor activity in diabetic mice was also reduced by pretreatment with naltrindole, a selective delta-opioid receptor antagonist, and 7-benzylidenenaltrexone, a selective delta1-opioid receptor antagonist. The rate of dopamine turnover in the limbic forebrain in diabetic mice was significantly higher than that in non-diabetic mice. These findings suggest that the enhanced spontaneous locomotor activity in diabetic mice may result from increased dopamine neurotransmission, which might be due to an increase in dopamine release in mesolimbic dopamine systems. The increased dopamine neurotransmission in diabetic mice may also be due to the up-regulation of delta-opioid receptor-mediated functions.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1994

Antitussive effect of dihydroetorphine in mice.

The present study examined the opioid receptors involved in the antitussive effect of dihydroetorphine in mice. Dihydroetorphine suppressed coughs dose dependently at doses between 0.1-1 micrograms/kg i.p. Blockade of mu-opioid receptors by pretreatment with beta-funaltrexamine significantly reduced the antitussive effect of dihydroetorphine. Furthermore, the antitussive effect of dihydroetorphine was also antagonized by nor-binaltorphimine, a kappa-opioid receptor antagonist. However, pretreatment with naltrindole, a delta-opioid receptor antagonist, did not affect the antitussive effect of dihydroetorphine. These results indicate that the antitussive effect of dihydroetorphine is mediated by the activation of mu-opioid receptors and of kappa-opioid receptors, but not delta-opioid receptors.

Alkylating Agents↗
PubMed1994

Decrease in vasodilator effects of platelet-activating factor in resistance vessels of spontaneously hypertensive rats.

We studied the endothelium-dependent vasodilator effects of platelet-activating factor (PAF) on the mesenteric arterial bed of Wistar Kyoto rats (WKYs) and spontaneously hypertensive rats (SHRs) and found that vasodilation induced by PAF was significantly attenuated in SHRs. We discovered no significant differences in reactivity or sensitivity of the mesentery to acetylcholine between WKYs and SHRs. Our results strongly suggest that the attenuated vasodilator effects of PAF on the SHR mesenteric arterial bed may be due in part to desensitization rather than impairment of the endothelium.

Animals↗