[Effect of cholestyramine on angiopathies in cholesterol-fed mice and diabetic mice].
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Animals↗
Biomedical subjects
Y Kasuya
Publications and source records attributed to Y Kasuya.
[Endothelium-dependent relaxation response to cyclopiazonic acid in rat mesenteric arterial bed].
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Acetylcholine↗
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↗
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↗
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↗
[Case of kidney cancer presenting an interesting example of paraneoplastic syndrome].
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Aged↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗