Biomedical subjects

Y Kasuya

Publications and source records attributed to Y Kasuya.

At least 73 records · Page 4Linked to original sources

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↗

PubMed1994

Determination of rhoifolin and daidzin in human plasma by high-performance liquid chromatography.

A method for determining flavonoids in human plasma is presented for application to pharmacokinetic studies of two flavonoids, rhoifolin and daidzin. Isocratic reversed-phase high-performance liquid chromatography (HPLC) was used with genistin as an internal standard and solid-phase extraction using a Sep-Pak C18 cartridge. The mobile phases were acetonitrile-0.1 M ammonium acetate solution (20:80, v/v) for rhoifolin and methanol-0.1 M ammonium acetate solution (33:67, v/v) for daidzin. The detection limits on-column were 2 ng for rhoifolin and 0.5 ng for daidzin.

Acetates↗

PubMed1994

Activin A stimulates mitogenesis in Swiss 3T3 fibroblasts without activation of mitogen-activated protein kinases.

Activin A stimulated DNA synthesis and transient c-fos expression in quiescent Swiss 3T3 fibroblasts. The activin A-induced DNA synthesis was dose-dependent with a half-maximal effect obtained at 0.3 nM. The maximal response obtained at 10 nM was comparable with that induced by 5 ng/ml basic fibroblast growth factor. Swiss 3T3 fibroblasts expressed abundant high affinity binding sites for 125I-labeled activin A with a Kd value of 0.63 nM and the number of binding sites at 24,000/cell. Northern blot analysis revealed that Swiss 3T3 fibroblasts express a high level of type II activin receptor mRNA. In an attempt to elucidate the mechanism of mitogenic action of activin A, we examined the effect of activin A on mitogen-activated protein kinase activation. Unexpectedly, however, activin A did not induce kinase activation under conditions in which basic fibroblast growth factor and endothelin-1 at similar or even less potent mitogenic concentrations did. Furthermore, activin A did not induce phosphorylation of the Erk2 species of mitogen-activated protein kinase. These observations strongly suggest that the activation of mitogen-activated protein kinase is not a necessary step for activin A-induced DNA synthesis in Swiss 3T3 fibroblasts.

3T3 Cells↗

PubMed1994

Antinociceptive effect of L-arginine in diabetic mice.

The antinociceptive effect of L-arginine in streptozotocin-induced diabetic mice was examined. Although s.c. administration of L-arginine produced a dose-dependent inhibition of the tail-flick response in both non-diabetic and diabetic mice, the antinociceptive response was greater in diabetic mice than in non-diabetic mice. The antinociceptive effects of L-arginine in both diabetic and non-diabetic mice were significantly antagonized by s.c. administration of naltrindole, a selective delta-opioid receptor antagonist. However, neither beta-funaltrexamine, a selective mu-opioid receptor antagonist, nor nor-binaltorphimin ++, a selective kappa-opioid receptor antagonist, significantly affected the antinociceptive effect of L-arginine in diabetic and non-diabetic mice. These results suggest that L-arginine produces a marked antinociceptive effect in diabetic mice through the activation of delta-opioid receptors.

Analgesics↗

PubMed1994

Antitussive effect of [Met5]enkephalin-Arg6-Phe7 in mice.

We examined the effect of [Met5]enkephalin-Arg6-Phe7 (MEAP) on the capsaicin-induced cough reflex in mice. Intracerebroventricular administration of MEAP significantly decreased the number of coughs in a dose-dependent manner. The antitussive effect of MEAP was blocked by nor-binaltorphimine, a selective kappa-opioid receptor antagonist. However, beta-funaltrexamine, a mu-opioid receptor antagonist, had no effect on the antitussive effect of MEAP. On the other hand, the antinociceptive effect of MEAP, as determined in the tail-flick test, was blocked by both nor-binaltorphimine and beta-funaltrexamine. Naltrindole, a delta-opioid receptor antagonist, had no effect on either the antitussive effect or the antinociceptive effect of MEAP. These data suggest that MEAP exerts its antitussive effect in mice through the stimulation of kappa-opioid receptors, whereas the antinociceptive effect of MEAP is mediated through the simulation of both kappa- and mu-opioid receptors.

Animals↗

PubMed1994

Involvement of delta 1-opioid receptor antagonism in the antitussive effect of delta-opioid receptor antagonists.

The effects of 7-benzylidenenaltrexone (BNTX), a selective delta 1-opioid receptor antagonist, and naltriben, a selective delta 2-opioid receptor antagonist, on the capsaicin-induced cough reflex were studied in mice. I.p. administration of BNTX in doses from 0.1 to 3.0 mg/kg reduced the number of coughs dose dependently. The antitussive effect of BNTX was antagonized by [D-Pen2,5]enkephalin (DPDPE), a selective delta 1-opioid receptor agonist, while [D-Ala2]deltorphin II, a selective delta 2-opioid receptor agonist, had no effect on the antitussive effect of BNTX. Pretreatment with nor-binaltorphimine, a selective kappa-opioid receptor antagonist, had no significant effect on the antitussive effect of BNTX. I.p. administration of naltriben, in doses of 1 and 3 mg/kg, also significantly decreased the number of coughs. Although the antitussive effect of naltriben was antagonized by nor-binaltorphimine, the antitussive effect of naltriben was not attenuated by either DPDPE or [D-Ala2]deltorphin II. The antitussive effects of neither BNTX nor naltriben were antagonized by beta-funaltrexamine, a selective mu-opioid receptor antagonist. Thus, it seems likely that the delta 1-opioid receptor antagonism may be involved in the antitussive effect of delta-opioid receptor antagonists.

Animals↗

PubMed1994

Antinociceptive effect of lipopolysaccharide from Pantoea agglomerans on streptozotocin-induced diabetic mice.

The antinociceptive effect of lipopolysaccharide from Pantoea agglomerans (LPSp) in streptozotocin-induced diabetic mice was examined. Although subcutaneous (s.c.) administration of LPSp produced a dose-dependent inhibition of the tail-flick response in both non-diabetic and diabetic mice, the antinociceptive response was greater in diabetic mice than in non-diabetic mice. The antinociceptive effects of LPSp in both diabetic and non-diabetic mice were significantly antagonized by s.c. administration of naltrindole, a selective delta-opioid receptor antagonist or nor-binaltorphimine, a selective kappa-opioid receptor antagonist, but not by beta-funaltrexamine, a selective mu-opioid receptor antagonist. These results suggest that LPSp produces a marked antinociceptive effect in diabetic mice through the activation of delta- and kappa-opioid receptors.

Analgesics↗

PubMed1994

Streptozotocin-induced diabetes selectively reduces antinociception mediated by mu 1-opioid receptors, but not that mediated by mu 2-opioid receptors.

We assessed the effect of naloxonazine, a selective mu 1-opioid receptor antagonist, on antinociception produced by intrathecal or intracerebroventricular injections of morphine in streptozotocin-induced diabetic mice. The antinociceptive effect of morphine (10 micrograms), administered i.c.v., was significantly less in diabetic mice than in non-diabetic mice. The antinociceptive effect of i.c.v. morphine was significantly reduced in both diabetic and non-diabetic mice following pretreatment with naloxonazine. There were no significant differences in the antinociceptive effect of morphine (1 microgram, i.t.) in diabetic and non-diabetic mice. Furthermore, naloxonazine had no significant effect on the antinociceptive effect of i.t. morphine in either diabetic or non-diabetic mice. On the other hand, the antinociceptive effects of i.c.v. and i.t. morphine were significantly reduced following pretreatment with beta-funaltrexamine, a selective mu-opioid receptor antagonist, in both diabetic and non-diabetic mice. In conclusion, mice with diabetes are selectively hyporesponsive to supraspinal mu 1-opioid receptor-mediated antinociception, but are normally responsive to activation of spinal mu 2-opioid receptors.

Analgesics↗

PubMed1994

Activation of human neutrophils by Arg-Gly-Asp-Ser immobilized on microspheres.

The adhesive interaction of cells with extracellular matrix components is essential for a variety of cellular functions, and is frequently mediated by a tetra peptide, Arg-Gly-Asp-Ser (RGDS), located within fibronectin and other proteins. In this study, the RGDS-mediated activation of polymorphonuclear leukocytes accompanied by phagocytosis was investigated using monodisperse polymeric microspheres carrying RGDS. The parent and Arg-Gly-Glu-Ser (RGES)-carrying microspheres, which have no adhesion activity, were employed as controls. The ingestion of microspheres into PMN was not enhanced by immobilizing RGDS. However, PMNs exhibited unique oxygen consumption and enhanced liberation of reactive oxygen when RGDS-carrying microspheres were phagocytosed. These PMN responses disappeared with the addition of soluble RGDS. Furthermore, cytochalasin D, which inhibits actin polymerization, showed a marked inhibitory effect on oxygen consumption in the RGDS-carrying microsphere system, as compared with those in other systems. These findings show that RGDS-carrying microspheres induced the biospecific activation of PMNs by the signal transduction via RGDS-integrin binding without alteration in the degree of phagocytosis.

Amino Acid Sequence↗

PubMed1994

Reduction in ATP-sensitive potassium channel-mediated antinociception in diabetic mice.

To test our hypothesis that the abnormally low efficacy of mu-opioid agonists in diabetic mice may be due to functional changes in ATP-sensitive potassium channels, we evaluated the effects of cromakalim on the tail-flick latencies in diabetic and non-diabetic mice. Anti nociceptive effects of morphine (10 micrograms, ICV) in diabetic mice were significantly less than that in non-diabetic mice. Morphine-induced antinociception in non-diabetic mice was antagonized by pretreatment with glibenclamide (30 micrograms, ICV), an ATP-sensitive potassium channel blocker. Cromakalim (0.3 and 1 micrograms, ICV) produced significant, dose-dependent antinociception in non-diabetic mice, which was significantly reduced by pretreatment with glibenclamide. However, cromakalim did not markedly affect the tail-flick latencies in diabetic mice, even at higher doses (3 micrograms, ICV). On the other hand, [D-Pen2,5]enkephaline (DPDPE, 5 micrograms, ICV), a selective delta-opioid receptor agonist, produced significant antinociception in both diabetic and non-diabetic mice. Since pretreatment with glibenclamide significantly reduced the antinociceptive effect of DPDPE in non-diabetic mice but not in diabetic mice, delta-opioid receptor-mediated antinociception in diabetic mice may be independent of potassium channels. These results suggest that dysfunction of ATP-sensitive potassium channels may contribute to the demonstrated poor antinociceptive response of diabetic mice to mu-opioid agonists.

Adenosine Triphosphate↗

PubMed1994

Involvement of adenosine A1 receptors in antitussive effect in mice.

The effects of N6-cyclohexyladenosine, a selective adenosine A1 receptor agonist, on the capsaicin-induced cough reflex in mice were examined. I.c.v. administration of N6-cyclohexyladenosine in doses that ranged from 0.03 to 0.3 nmol decreased the number of coughs in a dose-dependent manner. Pretreatment with 8-cyclopentyl-1,3-theophylline, a selective adenosine A1 receptor antagonist, significantly reduced the antitussive effect of N6-cyclohexyladenosine. On the other hand, CGS21680 (0.3 and 1 nmol, i.c.v.), a selective adenosine A2 receptor agonist, had no significant effect on the number of capsaicin-induced coughs. These data suggest that adenosine A1 agonists may have a marked antitussive effect in mice.

Adenosine↗

PubMed1994

Streptozotocin-induced diabetes selectively enhances antinociception mediated by delta 1- but not delta 2-opioid receptors.

We assessed the effect of diabetes on antinociception produced by intracerebroventricular injection of delta-opioid receptor agonists [D-Pen2,5]enkephalin (DPDPE) and [D-Ala2]deltorphin II. The antinociceptive effect of DPDPE (10 nmol), administered i.c.v., was significantly greater in diabetic mice than in non-diabetic mice. The antinociceptive effect of i.c.v. DPDPE was significantly reduced in both diabetic and non-diabetic mice following pretreatment with 7-benzylidenenaltrexone (BNTX), a selective delta 1-opioid receptor antagonist, but not with naltriben (NTB), a selective delta 2-opioid receptor antagonist. There were no significant differences in the antinociceptive effect of [D-Ala2]deltorphin II (3 nmol, i.c.v.) in diabetic and non-diabetic mice. Furthermore, the antinociceptive effect of i.c.v. [D-Ala2]deltorphin II was significantly reduced in both diabetic and non-diabetic mice following pretreatment with NTB, but not with BNTX. In conclusion, mice with diabetes are selectively hyper-responsive to supraspinal delta 1-opioid receptor-mediated antinociception, but are normally responsive to activation of delta 2-opioid receptors.

Analgesia↗

PubMed1994

Differential mediation of cold water swim stress-induced antinociception by delta-opioid receptor subtypes in diabetic mice.

The involvement of delta-opioid receptor subtypes in cold water swim stress (CWSS)-induced antinociception in diabetic mice was compared with that in non-diabetic mice. Three-minute swim stress produced significant antinociception in both diabetic and non-diabetic mice as determined by the tail-pinch test. However, the extent of CWSS-induced antinociception in diabetic mice was significantly greater than that in non-diabetic mice. Pretreatment with naltriben, a selective delta 2-opioid receptor antagonist, significantly attenuated CWSS-induced antinociception in both non-diabetic and diabetic mice. In contrast, although 7-benzylidenenaltrexone, a selective delta 1-opioid receptor antagonist, significantly attenuated CWSS-induced antinociception in diabetic mice, it had no effect in non-diabetic mice. These results suggest that CWSS-induced antinociception in non-diabetic mice is mediated by delta 2-opioid receptors, whereas CWSS-induced antinociception in diabetic mice is mediated by both delta 1- and delta 2-opioid receptors. Furthermore, the enhanced CWSS-induced antinociception in diabetic mice may be due to the activation of delta 1-opioid receptors.

Analgesia↗

PubMed1994

Evidence for differential modulation of mu-opioid receptor-mediated antinociceptive and antitussive activities by spleen-derived factor(s) from diabetic mice.

The effects of spleen-derived factor(s) from diabetic mice on the antinociceptive and antitussive effects of mu-opioid receptor agonists were examined in mice. The antinociceptive effects were examined 1 week after adoptive transfer of the supernatant of spleen cell homogenate (SSCH) from diabetic mice (SSCH-D). Naive mice which had been injected with SSCH-D were less sensitive to the antinociceptive effects of mu-opioid receptor agonists, such as morphine and [D-Ala2, N-MePhe4, Gly-ol5]enkephalin (DAMGO), than mice which had been injected with SSCH from non-diabetic mice. The antinociceptive effects of DAMGO was also significantly lower in naive mice injected with SSCH-D than in SSCH from non-diabetic mice (SSCH-ND)-treated naive mice, when assessed 2 weeks after adoptive transfer of SSCH. The sensitivity to the antinociceptive effect of [D-Pen2,5]enkephalin (DPDPE), a delta-opioid receptor agonist, was significantly enhanced 2 weeks, but not 1 week, after adoptive transfer of SSCH-D. On the other hand, adoptive transfer of SSCH-D to naive mice had no significant effect on the recipients' antitussive sensitivities to morphine and DAMGO when assessed 1 week after transfer of SSCH-D. However, when the antitussive effect was assessed 2 weeks after adoptive transfer of SSCH, the antitussive effect of DAMGO was significantly lower in naive mice injected with SSCH-D than in SSCH-ND-treated naive mice. The reduction in the antitussive effect of DAMGO in naive mice had been injected with SSCH-D 2 weeks before testing was abolished when they were pretreated with naltrindole, a selective delta-opioid receptor antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics↗

PubMed1994

Influence of the structure of support microspheres on leucocyte activation by RGDS-carrying microspheres.

A cell adhesive peptide, Arg-Gly-Asp-Ser (RGDS), enhances leucocyte response to stimuli when insolubilized or conjugated with proteins. In order to investigate the contribution of the microsphere structure to leucocyte response. RGDS was immobilized onto several polymeric microspheres. The respiratory burst of polymorphonuclear leucocytes (PMNs) contacting contacting microspheres was enhanced by RGDS in cases where it was immobilized on polystyrene and, more effectively, a positively charged one. This was not observed in polyacrylamide-based or negative-charged microsphere systems. These results demonstrate that the property of supports strongly affects the regulation of the PMN response via an adhesive interaction.

Amino Acid Sequence↗

PubMed1994

Loss of contractile activity of endothelin-1 induced by electrical field stimulation-generated free radicals.

1. Electrical field stimulation (EFS; 10 V, 10 Hz, 2 ms) of porcine coronary artery strips precontracted with 10 nM endothelin-1 (ET-1) for 5 min caused a biphasic response, consisting of a slight contraction during EFS and a marked and irreversible relaxation just after EFS. This irreversible relaxation after EFS has never been investigated. In the present study, we have investigated the mechanism of the relaxation after EFS. 2. The EFS-induced response was not affected by the presence or absence of endothelium and was insensitive to 10 microM tetrodotoxin (TTX). 3. In the presence of free radical scavengers (40 u ml-1 superoxide dismutase (SOD), 1200 u ml-1 catalase or 80 mM D-mannitol), the relaxation after EFS was significantly inhibited. Moreover, relaxation after EFS was not observed in porcine coronary artery strips precontracted with 20 mM KCl. 4. In a cascade experiment, EFS of Krebs-Ringer solution containing 10 nM ET-1 induced marked suppression of the contractile activity of ET-1 in porcine coronary artery strips, which was in accord with the observed decrease in release of immunoreactive ET-1 (ir-ET-1). This effect of EFS was significantly inhibited by each of the free radical scavengers, 3 mM vitamin C, 40 u ml-1 SOD, 1200 u ml-1 catalase and 80 mM D-mannitol. 5. The exchange of 95% O2/5% CO2 gas for 95% N2/5% CO2 gas significantly inhibited the EFS-induced decrease in release of ir-ET-1. 6. Neither superoxide anions generated by xanthine (10 JM) plus xanthine oxidase (0.1 micro ml-1) nor hydrogen peroxide (10 microM) exogenously added to Krebs-Ringer solution containing 10 nM ET-1 affected the level of ir-ET-1.7. Generation of hydroxyl radicals was detected in the EFS-applied Krebs-Ringer solution. The EFS-induced generation of hydroxyl radicals was dependent on the period of stimulation and 02-bubbling, and significant generation of hydroxyl radicals was detectable with stimulation of over 5 min.Moreover, hydroxyl radicals generated in 50 mM NaCl solution containing 10 nM ET-1 by H202 plus Fe2 , i.e. the Fenton reaction, significantly decreased the level of ir-ET-l.8. These findings suggest that oxygen-derived hydroxyl radicals generated by EFS of porcine coronary artery strips inactivate ET-1, probably by structural modification. Thus, porcine coronary artery strips precontracted with ET-1 are potently relaxed by EFS.

Animals↗

PubMed1994

Suppression of hyperalgesia in streptozotocin-induced diabetic mice by a lipopolysaccharide from Pantoea agglomerans.

The ability of a lipopolysaccharide from Pantoea agglomerans (LPSp) to relieve hyperalgesia was examined by observing its inhibition of the decrease in the threshold for nociceptive perception, as determined by the tail-pinch test, in streptozotocin-induced diabetic mice. Subcutaneous injection of LPSp suppressed hyperalgesia in streptozotocin-induced diabetic mice and also exerted a therapeutic effect on hyperalgesia in these animals. The present data suggest that LPSp may be effective in relieving the pain associated with diabetic neuropathy.

Animals↗

PubMed1994

[Objective and subjective response in stage D2 prostate cancer patients with cancer pain].

Fourty-eight patients with stage D2 prostate cancer, initially treated with endocrine therapy at the University of Tokyo between 1981 and 1990, were followed up and analysed. For the assessment of a subjective response, pain score, narcotic score, and performance stages (PS) were used. Of the fourty-eight patients, twenty-one suffered from cancer pain due to bone metastases. These patients showed significantly (p < 0.01) more lesions of bone metastases and higher PS, compared with patients without cancer pain. The progression free survival of these patients was significantly (p < 0.01) lower than that of patients without cancer pain, although the actuarial survival was not significant. In twenty-one patients with cancer pain, the objective and subjective response rates to endocrine therapy were 75% and 86%, respectively. The duration of pain relief was 1.25-54 (median 19) months. Those rates to anti-cancer chemotherapy in refractory patients (8 patients) previously treated with endocrine therapy were both 25% and those to additional administration of flutamide (FUL) or diethylstilbestrol (DES) in refractory patients (6 patients) were 33% and 100%, respectively. Although the duration of pain relief was 0.78-8 (median 2) months, the additional administration of DES or FLU led to pain relief and improved quality of life (QOL) in all 6 patients. Endocrine therapy such as LH-RH agonist and non-steroidal pure anti-androgen, which has no severe side effects, would be of great usefulness in stage D2 prostatic cancer patients with pain on the basis of efficacy and safety.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗