Biomedical subjects

Y Kasuya

Publications and source records attributed to Y Kasuya.

At least 109 records · Page 6Linked to original sources

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↗

PubMed1994

Vasodilator effects of clonidine on the mesenteric arterial beds in normotensive and spontaneously hypertensive rats.

Clonidine, an alpha 2-agonist, caused a concentration-dependent vasodilation of the mesenteric arterial beds in both normotensive and hypertensive rats. The clonidine-induced vasodilation was inhibited by NG-nitro-L-arginine, and the inhibition was reversed by L-arginine. The concentration-dependent vasodilation was not significantly different between normotensive and hypertensive rats. These results suggest that clonidine has an endothelium-dependent vasorelaxant action in the resistance artery such as rat mesenteric arterial bed, and the endothelium-dependent vasodilator effects of clonidine in the mesentery may be involved in the depressor effect of the drug.

Animals↗

PubMed1994

Antitussive effect of (+/-) pentazocine in diabetic mice is mediated by delta-sites, but not by mu- or kappa-opioid receptors.

The effects of streptozotocin-induced diabetes on the antitussive effect of (+/-) pentazocine were examined in mice. Intracerebroventricular (i.c.v.) administration of (+/-) pentazocine produced a dose-dependent antitussive effect in both diabetic and non-diabetic mice. There were no significant differences in the antitussive effect of (+/-) pentazocine in diabetic and non-diabetic mice. The antitussive effect of i.c.v. (+/-) pentazocine was partially, but significantly, reduced in non-diabetic mice following pretreatment with either beta-funaltrexamine, a selective mu-opioid antagonist, or rimcazole, a specific sigma-site antagonist. The antitussive effect of (+/-) pentazocine in diabetic mice was significantly antagonized by pretreatment with rimcazole. However, beta-funaltrexamine had no effect on the antitussive effect of (+/-) pentazocine in diabetic mice. Furthermore, nor-binaltorphimine, a selective kappa-opioid receptor antagonist, had no significant effect on the antitussive effect of (+/-) pentazocine in either non-diabetic or diabetic mice. These results suggest that although the antitussive effect of i.c.v. (+/-) pentazocine in non-diabetic mice is mediated by both mu-opioid receptors and sigma-sites, in diabetic mice this effect is mainly mediated by sigma-sites.

Animals↗

PubMed1994

Effects of diabetes on the antinociceptive effect of (+/-)pentazocine in mice.

The antinociceptive effect of (+/-)pentazocine was examined in streptozotocin-induced diabetic mice. Although intracerebroventricular (i.c.v.) administration of (+/-)pentazocine (10 nmol) produced a significant antinociceptive effect in both non-diabetic and diabetic mice, the antinociceptive effect of (+/-)pentazocine was greater in diabetic mice than in non-diabetic mice. The antinociceptive effects of (+/-)pentazocine in both diabetic and non-diabetic mice were significantly antagonized by s.c. administration of nor-binaltorphimine, a selective kappa-opioid receptor antagonist. On the other hand, the antinociceptive effects of (+/-)pentazocine were potentiated when non-diabetic mice were pretreated with beta-funaltrexamine, a selective mu-opioid receptor antagonist. Furthermore, there was no significant difference in the antinociceptive effect of (+/-)pentazocine between diabetic mice and beta-funaltrexamine-treated non-diabetic mice. These results suggest that the hypo-responsiveness of mu-opioid receptors may account for the enhanced kappa-opioid receptor-mediated antinociceptive effect of (+/-)pentazocine in diabetic mice.

Analgesics↗

PubMed1994

[Stable isotope methodology in the pharmacokinetic study of steroids].

Stable isotopically labeled steroids can, without radiation hazards, be safely used as biological internal standards to perform pharmacokinetic studies of steroids in man. This technique offers an advantage in that an endogenous steroid and its stable isotopically labeled analogue exogenously administered can be differentiated easily by employing mass spectrometry. For example, we can examine the pharmacokinetics of cortisol and investigate the metabolic conversion of cortisol to cortisone in man by administering deuterium-labeled cortisol to human subjects as a tracer. The number and the stability of the label are fundamental requisites in stable isotope methodology. Successful application of methodology with stable isotopes is then always dependent on the availability of compounds that are labeled at predesignated chemically inert positions.

Adolescent↗

PubMed1993

Antitussive effects of naltrindole, a selective delta-opioid receptor antagonist, in mice and rats.

The effects of naltrindole, a selective delta-opioid receptor antagonist, on the capsaicin-induced cough reflex in mice and rats were studied. Intraperitoneal administration of naltrindole decreased the number of coughs both in mice and rats dose dependently. The cough-depressant effects reached a peak 15 min after the administration of naltrindole and lasted more than 120 min. Pretreatment with [D-Pen2,D-Pen5]enkephalin, a selective delta-opioid receptor agonist, partially but significantly reduced the antitussive effect of naltrindole. Blockade of kappa-opioid receptors by pretreatment with nor-binaltorphimine also partially antagonized the antitussive effect of naltrindole. However, the antitussive effect of naltrindole was not antagonized by beta-funaltrexamine, a selective mu-opioid receptor antagonist. Thus, it is possible that the antitussive effect of naltrindole may be mediated, in part, by kappa-opioid receptors. The present results provide evidence for the development of delta-opioid antagonists, especially naltrindole, for use as antitussive drugs.

Animals↗

PubMed1993

Effects of rimcazole, a specific antagonist of sigma sites, on the antitussive effects of non-narcotic antitussive drugs.

We examined the effects of rimcazole, a specific antagonist of sigma sites, on the antitussive effects of dextromethorphan and noscapine in mice. Intraperitoneal injection of rimcazole, in doses from 1 to 10 mg/kg, significantly and dose dependently antagonized the cough depressant effect of N,N'-di(orthotolyl)guanidine (DTG), a sigma ligand. The cough depressant effects of dextromethorphan (3 mg/kg i.p.) and noscapine (10 mg/kg i.p.) were also significantly and dose dependently reduced by pretreatment with rimcazole. However, rimcazole (10 mg/kg i.p.) did not have a significant effect on the antitussive effect of morphine (3 mg/kg i.p.). Furthermore, rimcazole by itself (10 and 30 mg/kg i.p.) had no significant effect on the number of coughs. These results suggest that sigma sites may be involved in the antitussive mechanism of centrally acting non-narcotic antitussive drugs.

Animals↗

PubMed1993

Simultaneous measurement of vasodilation and changes in cyclic nucleotides in the perfused mesenteric arterial bed of the rat.

We examined the relationship between relaxation responses of the mesenteric arterial bed and the levels of cAMP and cGMP released from the rat mesenteric arterial bed. Perfusions of mesentery preparations with 1 microM acetylcholine, 0.1 microM calcium ionophore A23187, and 1 microM sodium nitroprusside all produced complete and long-lasting relaxation and increased the levels of cAMP as well as cGMP in the effluent. In endothelium-denuded preparations, acetylcholine did not elicit either vasorelaxation or an increase in cAMP and cGMP levels. Perfusion of the endothelium-denuded preparation with 1 microM sodium nitroprusside evoked complete relaxation and a marked increase in cGMP levels but not cAMP levels. Isoproterenol (1 microM) produced complete relaxation and an increase in cAMP levels, but did not affect cGMP levels either in the preparation with or in that without endothelium. Acetylcholine (0.001-1 microM) relaxed the preparation and increased cAMP and cGMP levels in the effluent in a dose-dependent manner. The acetylcholine-induced relaxation was reversed by 45% following perfusion with 10 microM methylene blue, and both the cAMP and cGMP levels were decreased. L-NG-Monomethyl arginine (L-NMMA) (100 microM), a nitric oxide synthase inhibitor, completely reversed the relaxation induced by 0.1 microM acetylcholine and reduced the elevated cGMP levels. Indomethacin (1 microM) reduced the acetylcholine-induced cAMP release, but did not alter the vasorelaxation in response to acetylcholine. We propose a novel method for the simultaneous measurement of vasodilation and changes in cAMP and cGMP levels released from the rat mesenteric arterial bed. We conclude that this method may provide information about the function of the endothelium of resistance vessels.

Acetylcholine↗

PubMed1993

The effects of cyclosporine on morphine-induced antinociception in diabetic mice.

The effects of cyclosporine on the antinociceptive effect of morphine were examined in diabetic mice. Sensitivities to the antinociceptive effect of morphine (5 mg/kg s.c.) in diabetic mice which had been pretreated with cyclosporine (30 mg/kg per day s.c.) for 14 days returned to those in vehicle-treated nondiabetic mice. Naive mice which had been injected with the supernatant of spleen cell homogenate (SSCH) from vehicle-treated diabetic mice were less sensitive to morphine-induced antinociception. However, adoptive transfer of SSCH from cyclosporine-treated diabetic mice to naive mice had no effect on the recipients' antinociceptive sensitivities to morphine. These results suggest that the abnormal antinociceptive effect of morphine and the immune responses of diabetic mice may somehow be related.

Analgesics↗

PubMed1993

Effect of diabetes on the antinociceptive effect of beta-endorphin.

We examined whether streptozotocin-induced diabetes can modulate beta-endorphin-induced antinociception in mice. While beta-endorphin administered i.c.v. produced a dose-dependent inhibition of the tail-flick response in both diabetic and non-diabetic mice, the antinociceptive response was greater in diabetic mice than in non-diabetic mice. The ED50 value of beta-endorphin administered i.c.v. in diabetic mice was significantly lower than that in non-diabetic mice. The antinociceptive effects of beta-endorphin administered i.c.v. in both diabetic and non-diabetic mice were significantly antagonized by s.c. administration of naltrindole, a selective delta-opioid receptor antagonist. beta-Endorphin administered i.t. also produced a dose-dependent antinociception in both diabetic and non-diabetic mice. However, the ED50 value of kappa-opioid receptor antagonist. On the other hand, the antinociceptive potency of DPDPE, a selective delta-opioid agonist, administered i.t. is significantly increased in diabetic mice, as compared with non-diabetic mice, whereas, the antinociceptive potency of U-50,488H, a kappa-opioid receptor agonist, administered i.t. is significantly less than in non-diabetic mice. These results suggest that diabetes may modulate beta-endorphin-induced antinociception differently at the spinal and supraspinal levels.

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