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Biomedical subjects

Y Kasuya

Publications and source records attributed to Y Kasuya.

At least 19 recordsLinked to original sources
PubMed1995

Involvement of delta 1-opioid receptors in the antinociceptive effects of mexiletine in mice.

The mechanisms of the antinociceptive effect of mexiletine were assessed by administering selective mu-, delta- and kappa-opioid receptor antagonists in diabetic and non-diabetic mice. Intraperitoneal administration of mexiletine, at doses of 10 and 30 mg/kg, produced dose-dependent antinociception in the tail-pinch test in both non-diabetic and diabetic mice. The antinociceptive effect of mexiletine in diabetic mice was significantly greater than that in non-diabetic mice. The antinociceptive effect of mexiletine did not result from the activation of mu- or kappa-opioid receptors in either non-diabetic or diabetic mice, since treatment with either beta-funaltrexamine, a selective mu- opioid receptor antagonist, or nor-binaltorphimine, a selective kappa-opioid receptor antagonist, was ineffective in blocking mexiletine-induced antinociception. The antinociceptive effect of mexiletine was significantly antagonized by naltrindole, a selective delta-opioid receptor antagonist, in both non-diabetic and diabetic mice. Furthermore, the antinociceptive effect of mexiletine was significantly reduced in both non-diabetic and diabetic mice following pretreatment with 7-benzylidenenaltrexone, a selective delta 1-opioid receptor antagonist, but not with naltriben, a selective delta 2-opioid receptor antagonist. These result suggest that delta 1-opioid receptor-mediated mechanisms may be involved in the antinociceptive effect of mexiletine.

Animals↗
PubMed1995

Antinociceptive effects of the selective non-peptidic delta-opioid receptor agonist TAN-67 in diabetic mice.

The antinociceptive potencies of 2-methyl-4 alpha alpha-(3-hydroxyphenyl)-1,2,3,4,4a,5,12,12 alpha alpha-octahydro-quinolino[2,3,3-g]isoquinoline (TAN-67), a non-peptidic delta-opioid receptor agonist, were examined using the acetic acid abdominal constriction test and the tail-flick test in diabetic mice. TAN-67, at doses of 3-100 mg/kg, s.c. [corrected], produced a marked and dose-dependent inhibition of the number of acetic acid-induced abdominal constrictions in both non-diabetic and diabetic mice. The antinociceptive effect of TAN-67 in the acetic acid abdominal constriction test in diabetic mice was greater than that in non-diabetic mice. Indeed, the ED50 (95% confidence limits) value of TAN-67 for the inhibition of acetic acid-induced abdominal constrictions in diabetic mice (6.0 (3.5-10.5) mg/kg) was significantly lower than that in non-diabetic mice (31.4 (14.2-69.4) mg/kg). The antinociceptive effect of TAN-67 was not antagonized by pretreatment with either beta-funaltrexamine, a selective mu-opioid receptor antagonist, or nor-binaltorphimine, a selective kappa-opioid receptor antagonist. When 7-benzylidenenaltrexone (0.3 mg/kg, s.c.), a selective delta 1-opioid receptor antagonist, was administered 10 min before treatment with TAN-67, the antinociceptive effect of TAN-67 was significantly antagonized. However, naltriben, a selective delta 2-opioid receptor antagonist, had no significant effect on the antinociceptive effect of TAN-67. Furthermore, in the tail-flick test, TAN-67 at doses of 3-30 mg/kg, s.c. [corrected], also produced a marked and dose-dependent antinociceptive effect in diabetic mice, but not in non-diabetic mice. In conclusion, TAN-67 produced an antinociceptive effect through the activation of delta 1-opioid receptors. Furthermore, the results of this study support our hypothesis that mice with diabetes are selectively hyperresponsive to delta 1-opioid receptor-mediated antinociception.

Analgesics↗
PubMed1995

Antinociceptive effect of dihydroetorphine in diabetic mice.

The antinociceptive potency of dihydroetorphine in diabetic mice was examined. Subcutaneous administration of dihydroetorphine produced a dose-dependent antinociception in both non-diabetic and diabetic mice. The antinociceptive potency of s.c. dihydroetorphine was less in diabetic mice than in non-diabetic mice. The antinociception induced by i.c.v. dihydroetorphine (0.02 microgram) was also significantly less in diabetic mice than in non-diabetic mice. The antinociceptive effects of dihydroetorphine (10 micrograms/kg i.p.) in both diabetic and non-diabetic mice were significantly antagonized by s.c. administration of beta-funaltrexamine, a selective mu-opioid receptor antagonist. Furthermore, the antinociceptive effect of dihydroetorphine (10 micrograms/kg i.p.) in non-diabetic mice, but not in diabetic mice, was also significantly antagonized by naloxonazine, a selective mu 1-opioid receptor antagonist. The time course and the potency of the antinociceptive effect of dihydroetorphine (10 micrograms/kg i.p.) in diabetic mice were similar to those in naloxonazine-treated non-diabetic mice. Naltrindole, a selective delta-opioid receptor antagonist, or nor-binaltorphimine, a selective kappa-opioid receptor antagonist, had no significant effect on the antinociceptive effect of dihydroetorphine (10 micrograms/kg i.p.) in both diabetic and non-diabetic mice. These results suggest that dihydroetorphine produces an antinociceptive effect through the activation of both mu 1- and mu 2-opioid receptors in mice. Furthermore, the reduction in dihydroetorphine-induced antinociception in diabetic mice, as compared with non-diabetic mice, may be due to the hyporesponsive to supraspinal mu 1-opioid receptor-mediated antinociception in diabetic mice.

Analgesia↗
PubMed1995

Molecular identification of guanine-nucleotide-binding regulatory proteins which couple to endothelin receptors.

The coupling of two endothelin receptor subtypes (ET(A) and ETB) to several types of guanine-nucleotide-binding regulatory protein (G protein) was examined. Two subtypes of receptor cDNAs were transfected alone or together with four different G protein alpha subunit cDNAs in COS-7 cells. In ET(A) receptor-transfected cells, endothelin-1 (ET-1) activated phosphatidylinositol-specific phospholipase C as measured by the production of phosphatidylinositol 1,4,5-trisphosphate [Ins(1,4,5)P3]. ETB-receptor-transfected cells also produced Ins(1,4,5)P3 on stimulation by ET-1. The ET-1-induced production of Ins(1,4,5)P3 was markedly higher in G alpha q-cotransfected or G alpha 11-cotransfected cells than in cells transfected with each receptor alone. ET-1 also stimulated production of cAMP in ET(A) or ETB receptor-transfected cells. The production of cAMP was synergistically amplified by G alpha s co-transfection with each receptor. In contrast, when G alpha i2 was co-transfected with the ET(A) or ETB receptor, ET-1 displayed an inhibitory action on forskolin-stimulated cAMP accumulation. Pertussis-toxin treatment of the G alpha i2-transfected cells resulted in abolition of the endothelin-induced inhibition of cAMP accumulation. These observations indicate that both ET(A) and ETB receptors are able to couple to Gq, G11, Gs and Gi2, and suggest that endothelin receptors stimulate multiple effectors via several types of G protein simultaneously. The overall effects induced by endothelin may differ in cell types depending on the level of expression of each G-protein subtype in the cell.

Animals↗
PubMed1995

Expression of a cell adhesion molecule, neuropilin, in the developing chick nervous system.

Neuropilin (previously known as the A5 protein) is a membrane protein identified in Xenopus and is presumed to be involved in the target recognition of the optic nerve fibers. We have isolated cDNAs encoding the chick homologue of neuropilin, using the Xenopus neuropilin cDNA as a hybridization probe. The predicted amino acid sequence of chick neuropilin is 75% identical to that of the Xenopus homologue. A cell aggregation assay showed that fibroblasts transfected with the chick neuropilin cDNA acquired cell adhesiveness. This adhesion is mediated by a heterophilic interaction between neuropilin and protease-sensitive molecules on fibroblasts. The expression of chick neuropilin is restricted to certain neuronal circuits and is dynamically regulated during development, as is the Xenopus homologue. However, their expression patterns differed significantly in the visual systems between the two species: In the chick optic tectum, the localization of neuropilin is confined to layers d and e of SGFS, two of the six layers receiving the retinal input; the chick optic nerve fibers do not express neuropilin; in the chick retina, amacrine cells transiently express neuropilin. Cultured neurons of the dorsal root ganglia express chick neuropilin on their neurites including growth cones. These results suggests that neuropilin functions as a cell adhesion molecule during the formation of certain neuronal circuits in vivo.

3T3 Cells↗
PubMed1995

Endothelium-derived hyperpolarizing factor does not contribute to the decrease in endothelium-dependent relaxation in the aorta of streptozotocin-induced diabetic rats.

1. We examined the contribution of endothelium-derived hyperpolarizing factor (EDHF) to the impairment of endothelium-dependent relaxation caused by acetylcholine (ACh) in the aorta of streptozotocin-induced diabetic rats, by using N omega-L-nitro-arginine methylester (L-NAME) and tetraethylammonium chloride (TEA) to inhibit nitric oxide (NO) and EDHF, respectively. 2. ACh-induced relaxation of the aorta decreased in diabetic rats. In contrast, sodium nitroprusside-induced relaxation was the same in diabetic rats and control rats. 3. Treatment with 5 x 10(-7) M L-NAME resulted in a right shift of the dose-response curves of ACh-induced relaxation in the aorta. The shift was greater in the control aorta. 4. Treatment with 5 x 10(-4) M TEA resulted in a similar right shift in both the control and diabetic aorta. 5. Therefore, while endothelium-derived NO appears to contribute to the impairment of ACh-induced endothelium-dependent relaxation in the aorta of diabetic rats, EDHF does not.

Acetylcholine↗
PubMed1995

Cardiovascular selectivity of 1,4-dihydropyridine derivatives, efonidipine (NZ-105), nicardipine and structure related compounds in isolated guinea-pig tissues.

1. The cardiovascular selectivities of 1,4-dihydropyridine derivatives, efonidipine (NZ-105), nicardipine, 3NZ5NIC (the drug with NZ-105-type side-chain at C3 position and nicardipine-type at C5) and 3NIC5NZ (the drug with nicardipine-type side chain at C3 and NZ-105-type at C5) were studied in vitro. 2. All four compounds caused relaxation of guinea-pig aortae precontracted with a high K+. The pEC50 values were 7.5, 8.3, 8.1 and 5.6, for NZ-105, nicardipine, 3NIC5NZ and 3NZ5NIC, respectively. The relaxation produced by NZ-105 was slower in onset than those produced by the other compounds. The rate constant K(hr-1) of the relaxations were 0.59, 1.31, 1.02 and 1.24, for NZ-105, nicardipine, 3NIC5NZ and 3NZ5NIC, respectively. 3. In the electrically paced guinea-pig papillary muscles, NZ-105, 3NIC5NZ and 3NZ5NIC, even at concentrations as high as 10(-6) M, slightly decreased the contractile force (by 44.9 +/- 7.1%, 58.6 +/- 5.4% and 52.2 +/- 3.9%, respectively), whereas 10(-6) M nicardipine decreased the force by 84.9 +/- 3.3%. The negative inotropic effect of NZ-105 and 3NIC5NZ, but not that of 3NZ5NIC or nicardipine, was over 10 times weaker than their vasorelaxant effect. 4. In the guinea-pig right atria, NZ-105 and nicardipine at 10(-8) M decreased the spontaneous contraction rate by 67.9 +/- 15.0% and 39.7 +/- 15.4%, respectively. 3NIC5NZ at 3 x 10(-9) M and 3NZ5NIC at 3 x 10(-8) M had little effect on the rate, whereas 10(-8) M 3NIC5NZ and 10(-7) M 3NZ5NIC arrested the beating within 3 hr after administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Plexin: a novel neuronal cell surface molecule that mediates cell adhesion via a homophilic binding mechanism in the presence of calcium ions.

Plexin (previously referred to as B2) is a neuronal cell surface molecule that has been identified in Xenopus. cDNA cloning reveals that plexin has no homology to known neuronal cell surface molecules but possesses, in its extracellular segment, three internal repeats of cysteine clusters that are homologous to the cysteine-rich domain of the c-met proto-oncogene protein product. The exogenous plexin proteins expressed on the surfaces of L cells by cDNA transfection mediate cell adhesion via a homophilic binding mechanism, under the presence of calcium ions. Plexin is expressed in the receptors and neurons of particular sensory systems. These findings indicate that plexin is a novel calcium-dependent cell adhesion molecule and suggest its involvement in specific neuronal cell interaction and/or contact.

Amino Acid Sequence↗
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↗
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↗
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↗