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Biomedical subjects

M Asano

Publications and source records attributed to M Asano.

At least 163 records · Page 9Linked to original sources
PubMed1997

Potent vasoconstrictor actions of cyclopiazonic acid and thapsigargin on femoral arteries from spontaneously hypertensive rats.

1. Ca2+ buffering function of sarcoplasmic reticulum (SR) in the resting state of arteries from spontaneously hypertensive rats (SHR) was examined. Differences in the effects of cyclopiazonic acid (CPA) and thapsigargin, agents which inhibit the Ca(2+)-ATPase of SR, on tension and cellular Ca2+ level were assessed in endothelium-denuded strips of femoral arteries from 13-week-old SHR and normotensive Wistar-Kyoto rats (WKY). 2. In resting strips preloaded with fura-PE3, the addition of CPA (10 microM) or thapsigargin (100 nM) caused an elevation of cytosolic Ca2+ level ([Ca2+]i) and a contraction. These responses were significantly greater in SHR than in WKY. 3. The additional of verapamil (3 microM) to the resting strips caused a decrease in resting [Ca2+]i, which was significantly greater in SHR than in WKY. In SHR, but not in WKY, this decrease was accompanied by a relaxation from the resting tone, suggesting the maintenance of myogenic tone in the SHR artery. 4. Verapamil (3 microM) abolished differences between SHR and WKY. The effects of verapamil were much greater on the contraction than on the [Ca2+]i. 5. The resting of Ca2+ influx in arteries measured after a 5 min incubation of the artery with 45Ca was not increased by CPA or thapsigargin in either SHR or WKY. The net Ca2+ entry measured after a 30 min incubation of the artery with 45Ca was decreased by CPA or thapsigargin in both SHR and WKY. The resting Ca2+ influx was significantly higher in SHR than in WKY, and was decreased by nifedipine (100 nM) in the SHR artery, but was unchanged in the WKY artery. 6. The resting 45Ca efflux from the artery was increased during the addition of CPA (10 microM). This increase was less in SHR than in WKY. The resting 45Ca efflux was the same in SHR and WKY. 7. These results suggest that (1) the Ca2+ influx via L-type voltage-dependent Ca2+ channels (VDCCs) was increased in the resting state of the SHR femoral artery, (2) the greater part of the increased Ca2+ influx was buffered by Ca2+ uptake into the SR and some Ca2+ reached the myofilaments resulting in the maintenance of the myogenic tone, and (3) therefore the functional elimination of SR by CPA or thapsigargin caused a large elevation of [Ca2+]i and a potent contraction in this artery. During this process, the contraction was mainly due to the basal Ca2+ influx via L-type VDCCs. The present study also showed the existence of a relatively large compartment of [Ca2+]i which does not contribute to the contraction during the addition of CPA or thapsigargin.

Animals↗
PubMed1997

The identification of an orally active, nonpeptide bradykinin B2 receptor antagonist, FR173657.

1. An orally active, nonpeptide bradykinin (BK) B2 receptor antagonist, FR173657 (E)-3-(6-acetamido-3-pyridyl)-N-[N-[2-4-dichloro-3-[(2-methyl-8-quinolin yl) oxymethyl]phenyl]-N-methylaminocarbonyl-methyl] acrylamide) has been identified. 2. This compound displaced [3H]-BK binding to B2 receptors present in guinea-pig ileum membranes with an IC50 of 5.6 x 10(-10) M and in rat uterus with an IC50 of 1.5 x 10(-9) M. It did not inhibit different specific radio-ligand binding to other receptor sites. 3. In human lung fibroblast IMR-90 cells, FR173657 displaced [3H]-BK binding to B2 receptors with an IC50 of 2.9 x 10(-9) M and a Ki of 3.6 x 10(-10) M, but did not reduce [3H]-des]Arg10-kallidin binding to B1 receptors. 4. In guinea-pig isolated preparations, FR173657 antagonized BK-induced contractions with an IC50 of 7.9 x 10(-9) M, but did not antagonize acetylcholine or histamine-induced contractions even at a concentration of 10(-6) M. FR173657 caused parallel rightward shifts of the concentration-response curves to BK at concentrations of 10(-9) M and 3.2 x 10(-9) M, and a little depression of the maximal response in addition to the parallel rightward shift of the concentration-response curve at a concentration of 10(-8) M. Analysis of the data yield a pA2 of 9.2 +/- 0.2 (n = 5) and a slope of 1.5 +/- 0.2 (n = 5). 5. In vivo, the oral administration of FR173657 inhibited BK-induced bronchoconstriction dose-dependently in guinea-pigs with an ED50 of 0.075 mg kg-1, but did not inhibit histamine-induced bronchoconstriction even at 1 mg kg-1. FR173657 also inhibited carrageenin-induced paw oedema with an ED50 of 6.8 mg kg-1 2 h after the carrageenin injection in rats. 6. These results show that FR173657 is a potent, selective, and orally active bradykinin B2 receptor antagonist.

Administration, Oral↗
PubMed1997

Inhibitory effects of omega-3 polyunsaturated fatty acids on receptor-mediated non-selective cation currents in rat A7r5 vascular smooth muscle cells.

1. The effects of omega-3 polyunsaturated fatty acids on receptor-mediated non-selective cation current (Icat) and K+ current were investigated in aortic smooth muscle cells from foetal rat aorta (A7r5 cells). The whole-cell voltage clamp technique was employed. 2. With a K(+)-containing solution, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA, 30 microM) produced an outward current at a holding potential of -40 mV. This response was inhibited by tetraethylammonium (20 mM) or Cs+ in the patch pipette solution, and the reversal potential of the EPA-induced current followed the K+ equilibrium potential in a near Nernstian manner. 3. Under conditions with a Cs(+)-containing pipette solution, both vasopressin and endothelin-1 (100 nM) induced a long-lasting inward current at a holding potential of -60 mV. The reversal potential of these agonist-induced currents was about +0 mV, and was not significantly altered by the replacement of the extracellular or intracellular Cl+ concentration, suggesting that the induced current was a cation-selective current (Icat). 4. La3+ and Cd2+ (1 mM) completely abolished these agonist-induced Icat, but nifedipine (10 microM) failed to inhibit it significantly. 5. omega-3 polyunsaturated fatty acids (3-100 microM), EPA, DHA and docosapentaenoic acids (DPA), inhibited the agonist-induced Icat in a concentration-dependent manner. The potency of the inhibitory effect was EPA > DHA > DPA, and the half maximal inhibitory concentration (IC50) of EPA was about 7 microM. 6. Arachidonic and linoleic acids (10, 30 microM) showed a smaller inhibitory effect compared to omega-3 fatty acids. Also, oleic and stearic acids (30 microM) did not show a significant inhibitory effect on Icat. 7. A similar inhibitory action of EPA was observed when Icat was activated by intracellularly applied GTP gamma S in the absence of agonists, suggesting that the site of action of omega-3 fatty acids is not located on the receptor. 8. These results demonstrate that omega-3 polyunsaturated fatty acids can activate a K+ current and also effectively inhibit receptor-mediated non-selective cation currents in rat A7r5 vascular smooth muscle cells. Thus, the data suggest that omega-3 fatty acids may play an important role in the regulation of vascular tone.

Animals↗
PubMed1997

Effects of a nonpeptide bradykinin B2 receptor antagonist, FR167344, on different in vivo animal models of inflammation.

1. The effects of a novel, potent and orally active nonpeptide bradykinin B2 receptor antagonist, FR167344 (N-[N-[3-[(3-bromo-2-methylimidazo[1,2-a]pyridin-8-yl)oxymethyl]-2 ,4-dichlorophenyl]-N-methylaminocarbonylmethyl]-4-(dimethylamin ocarbonyl) cinnamylamide hydrochloride) were tested in three different in vivo models of inflammation. 2. Oral administration of FR167344 inhibited carrageenin-induced paw oedema in rats (carrageenin: 1%, 0.1 ml per animal, intraplantar), with an ID50 of 2.7 mg kg(-1) at 2 h after carrageenin injection (n=10 or 11). 3. Oral administration of the compound also inhibited kaolin-induced writhing (kaolin: 250 mg kg(-1), i.p.) in mice, with ID50 of 2.8 mg kg(-1) in 10 min writhing and 4.2 mg kg(-1) in 15 min writhing (n=19 or 20). 4. Additionally, oral administration of FR167344 inhibited caerulein-induced pancreatic oedema with an ID50 of 13.8 mg kg(-1) as well as increases in amylase and lipase of blood samples with ID50 of 10.3 and 7.4 mg kg(-1), respectively, in rats (n=10). 5. These results show that FR167344 is an orally active, anti-inflammatory and anti-nociceptive agent in carrageenin-induced paw oedema, kaolin-induced writhing and caerulein-induced pancreatitis. FR167344 may have therapeutic potential against inflammatory diseases by oral administration and it may be a useful tool for studying the involvement of B2 receptors in various in vivo models of inflammation.

Administration, Oral↗
PubMed1997

The polymeric immunoglobulin receptor (secretory component) in a human intestinal epithelial cell line is up-regulated by interleukin-1.

Secretory component (SC or polymeric immunoglobulin receptor) on mucosal epithelial cells mediates transcytosis of polymeric immunoglobulin into external fluids and functions as a receptor for polymeric immunoglobulin. SC expression in a human colonic adenocarcinoma cell line, HT-29 has been reported to be up-regulated by various cytokines, such as interferon-gamma, tumour necrosis factor-alpha and interleukin-4 (IL-4). However, up-regulation of SC by IL-1 is controversial. In this study, we investigated the effect of human recombinant IL-1 alone on SC expression in HT-29 cells in detail. Immunocytochemistry and Northern blot analysis revealed that IL-1 beta increased both the number of SC-positive cells and SC mRNA expression. Enzyme-linked immunosorbent assay revealed that IL-1 beta enhanced secretion by HT-29 cells in both time- and dose-dependent manners. IL-1 alpha had the same effects on HT-29 cells. Northern blot analysis demonstrated that cycloheximide and actinomycin D abolished the effect of IL-1. Moreover, we detected IL-1 receptor (IL-1R) type I mRNA in HT-29 cells by polymerase chain reaction (PCR) and sequenced the PCR-amplified product. We think that it reflects the possibility of the presence of IL-1R in HT-29 cells. From these data, we concluded that IL-1 beta and IL-1 alpha play regulatory roles in SC expression, and their effects depend on de novo protein synthesis and transcription.

Blotting, Northern↗
PubMed1997

Molecular cloning and characterization of the promoter of the human N-methylpurine-DNA glycosylase (MPG) gene.

The promoter region of the human N-methylpurine-DNA glycosylase (MPG) gene was cloned and characterized. The cloned segment contains two first exons that were earlier identified and named exons 1a and 1b. These were found to be separated by approximately 800 bp. The minimal promoter region was identified upstream to the distal exon 1a, by transient transfection, and no promoter activity was found in the region in between exons 1a and 1b, suggesting that transcription starts at a single site which is then processed to generate mRNAs of the isoforms. The promoter sequence is G and C rich and contains neither TATA box, nor apparent CAAT sequences, although a partially matched CAAT sequence was identified just downstream to the minimal promoter.

Base Sequence↗
PubMed1997

Hemodynamic characterization of YM435, a novel dopamine DA1 receptor agonist, in anesthetized dogs.

The cardiovascular effects of YM435, a dopamine DA1 receptor agonist, were compared with those of dopamine in open-chest anesthetized dogs. Intravenous infusion of YM435 (0.1-3 microg/kg/min) increased renal blood flow and cardiac output and reduced renal vascular resistance and total peripheral vascular resistance, with a decrease in mean blood pressure, in a dose-dependent manner, with little change in heart rate. At 1 microg/kg/min i.v., renal blood flow increased by 20 +/- 7%, cardiac output increased by 14 +/- 6%, renal vascular resistance decreased by 22 +/- 4%, total peripheral vascular resistance decreased by 18 +/- 4%, and mean blood pressure decreased by 7 +/- 1%. The striking difference between the cardiovascular effects of YM435 and those of dopamine was that YM435 caused no vasoconstriction or increase in heart rate, even at high doses. The cardiovascular effects of YM435 (1 microg/kg/min i.v.) were almost completely inhibited by treatment with SCH 23390, a selective dopamine DA1 receptor antagonist. Furthermore, intravenous infusion of YM435 (0.1-3 microg/kg/min) dose-dependently reversed the increase in blood pressure and renal vascular resistance induced by angiotensin II or norepinephrine in closed-chest anesthetized dogs. Our results demonstrate that intravenous infusion of YM435 produces dose-dependent renal vasodilating and hypotensive effects by stimulation of dopamine DA1 receptors and suggest that YM435 may be useful for the parenteral treatment of acute elevation of blood pressure.

Angiotensin II↗
PubMed1997

Testosterone replacement therapy for male hypogonadism with a radiation-polymerized testicular prosthesis.

BACKGROUND: The effect of an artificial testicular prosthesis on sexual disturbance in hypogonadal men was investigated. METHODS: Twelve hypogonadal men were treated with testosterone replacement therapy delivered via radiation-polymerized testicular prostheses surgically implanted in their scrotums. RESULTS: An average serum testosterone level of over 200 ng/dL was maintained for 48 months. Most patients treated with this prosthesis were satisfied with the improvement of their sexual activity. Moreover, the patients were psychologically more satisfied with the enlarged scrotum achieved with the implanted prosthesis. CONCLUSION: We recommend this prosthesis as the first choice among testosterone-replacement therapies for hypogonadal men.

Adolescent↗
PubMed1997

Clinical, pathological, and etiologic aspects of acquired dermal melanocytosis.

To study the pathogenesis of acquired dermal melanocytosis (ADM), we reviewed the clinical, immunohistochemical, and ultrastructural features of 34 cases (female, 33, and male, 1) of ADM. The patients' ages at onset ranged from 8 to 51 years and averaged 26.8 +/- 12.7 years. There was a positive family history. Gray-brown macules were mostly recognized on the face. Not only active dermal melanocytes but also non-pigmented c-KIT- and TRP-2-positive immature melanocytes were detected in the dermis. Taken together those clinical and histological findings, activation of pre-existing immature melanocytes by sunlight, estrogen, and/or progesterone, and some other factors, may be the most likely mode of the development of ADM. Moreover, using cultured murine neural crest cells as a model of c-KIT-positive immature melanocytes, we confirmed that endothelin-1, which is produced and secreted by keratinocytes after UV-irradiation, affects melanocytes and accelerated melanogenesis.

Adult↗
PubMed1997

Novel subtype-selective nonpeptide bradykinin receptor antagonists FR167344 and FR173657.

We describe the receptor binding and antagonistic properties of two novel nonpeptide antagonists, FR167344 (3-bromo-8-[2,6-dichloro-3-[N-[(E)-4-(N,N-dimethylcarbamoyl)cinnamido acetyl]-N-methylamino]benzyloxy]-2-methylimidazo[1,2-a]pyridine hydrochloride) and FR173657 (8-[3-[N-[(E)-3-(6-acetamidopyridin-3-yl)acryloylglycyl]-N-m ethylamino]-2,6-dichlorobenzyloxy]-2-methylquinoline), for the human bradykinin receptor subtypes (B1 and B2). In competitive experiments using membranes prepared from Chinese hamster ovary cells expressing the bradykinin receptor subtypes, FR167344 and FR173657 showed a high affinity binding to the B2 receptor with IC50 values of 65 and 8.9 nM, respectively, and no binding affinity for the B1 receptor. FR167344 and FR173657 inhibited the B2 receptor-mediated phosphatidylinositol (PI) hydrolysis and produced a concentration-dependent rightward shift in the dose-response curve to bradykinin. This shift was accompanied by a progressive reduction of maximal response. Estimated pA2 values for the antagonism of bradykinin-induced PI hydrolysis by FR167344 and FR173657 were 8.0 and 9.0, respectively. FR167344 and FR173657 showed no stimulatory effects on PI hydrolysis. Therefore, FR167344 and FR173657 are potent, highly selective, and insurmountable antagonists for the human bradykinin B2 receptor.

Animals↗
PubMed1997

Nonpeptide mimic of bradykinin with long-acting properties at the bradykinin B2 receptor.

Kinins, members of a family of peptides released from kininogens by the action of kallikreins, exhibit a variety of biological activities including vasodilation, increased vascular permeability, contraction of smooth muscle cells, and activation of sensory neurons. However, investigation of the physiological actions of kinins has been greatly hampered because its effects are curtailed by rapid proteolysis in blood, lung, and liver. We describe the pharmacological characteristics of a novel nonpeptide bradykinin receptor agonist FR190997 (8-[2,6-dichloro-3-[N-[(E)-4-(N-methylcarbamoyl)cinnamidoacetyl ]-N-methylamino]benzyloxy]-2-methyl-4-(2-pyridylmethoxy)quinoli ne). FR190997 markedly stimulated phosphatidylinositol hydrolysis in Chinese hamster ovary cells permanently expressing the human bradykinin B2 receptor. The response of phosphatidylinositol hydrolysis was antagonized by the B2 receptor selective antagonist Hoe 140 (D-Arg-[hydroxyproline3,beta-thienylalanine4,D-Tic7,++ +Oic8]bradykinin). In competitive experiments using membranes prepared from Chinese hamster ovary cells expressing the human bradykinin receptor subtypes, FR190997 showed a high affinity binding to the B2 receptor with IC50 value of 5.3 nM and no binding affinity for the B1 receptor. In vivo, FR190997 mimics the biological action of bradykinin and induces hypotensive responses in rats with prolonged duration. Therefore, FR190997 is a highly potent and subtype-selective nonpeptide agonist which displays high intrinsic activity. This compound should represent a powerful tool for further investigation of the physiology and pathophysiology of bradykinin receptors.

Animals↗
PubMed1997

Cardiovascular effects of YM430, a 1,4-dihydropyridine derivative with beta-adrenoceptor blocking activity, in dogs and rats.

We evaluated the cardiovascular effects of YM430, a novel 1,4-dihydropyridine derivative with beta-adrenoceptor blocking activity, in dogs and rats. In anesthetized dogs, YM430 (0.01-0.3 mg/kg, i.v.) dose-dependently decreased mean blood pressure, total peripheral resistance and double product without increasing the heart rate. YM430 (0.01-0.3 mg/kg, i.v.) increased coronary artery as well as vertebral artery blood flow, whereas its effects on carotid, mesenteric, femoral and renal blood flow were small. At the same dose range as that which induced vasodilation effects, YM430 had little effect on the max. dp/dt or PQ-interval. In conscious dogs, YM430 (0.1-1 mg/kg, i.v.) produced dose-dependent hypotension with tachycardia. In conscious rats, oral dosing of YM430 (100 mg/kg p.o.) produced a long-lasting hypotensive effect with slight tachycardia. YM430 also inhibited isoproterenol (0.1 micrograms/kg i.v.)-induced tachycardia. These two effects of YM430 may be attributable to its calcium entry blocking and beta(1)-adrenoceptor blocking activity, respectively. The time course of the hypotensive (calcium entry blocking) effect of YM430 after oral dosing was very similar to that of its inhibition of isoproterenol-induced tachycardia (beta(1)-adrenoceptor blocking effect). These results indicate that the ratio of the two activities (calcium entry blocking and beta(1)-adrenoceptor blocking) of YM430 is constant after oral administration. In conclusion, YM430 could be both an antianginal and antihypertensive agent, because of its dual activities.

Adrenergic beta-Antagonists↗
PubMed1997

Studies on cardiac ingredients of plants. XIII: Chemical modification of gitoxin to cardiotonic compounds without vascular effect.

Nitrated gitoxins (4) and bufotoxin homologues with various lengths of alkyl chain at C-3 of the steroid nucleus (10) were prepared from gitoxin (1). The pharmacological activities of the resulting compounds (4 and 10) were evaluated by measurement of inhibitory effect on NA+, K(+)-adenosine triphosphatase (ATPase) prepared from dog kidney, positive inotropic effect (PIE) on isolated guinea-pig papillary muscle preparations, and the effect on smooth muscle using the mesenteric artery from spontaneously hypertensive rats. Most of the compounds showed a smaller contractile effect on the arterial muscle. Among these compounds, gitoxin 3"-nitrate (4g) exhibited the most desirable biological activities, such as PIE comparable to that of 1, 1.25 times wider concentration-dependent range than 1, and lack of contractile activity on vascular muscle.

Animals↗
PubMed1997

Characterization of 30-kDa fragments derived from beta-conglycinin degradation process during germination and seedling growth of soybean.

The degradation process of beta-conglycinin, a vicilin-type glycosylated storage protein of soybean seeds, during germination and seedling growth was examined by concanavalin A blotting combined with polyacrylamide gel electrophoresis. We detected and analyzed the structures of key intermediary fragments of 30 kDa derived from beta-conglycinin degradation, they were proved to be single-domain type subunits of beta-conglycinin. We show here a degradation process of beta-conglycinin: beta-conglycinin is subjected to limited proteolysis at exposed regions on the molecular surface, like domain junctions, generating 30-kDa single-domain fragments before non-specific proteolysis.

Amino Acid Sequence↗
PubMed1997

Consideration of the optimum pH for the analysis of serum p-phenylenediamine oxidase activity in thoroughbred horses.

The optimum pH for the measurement of serum p-phenylenediamine oxidase (Ox) activity was given (pH 6.6), and the relationship between serum ceruloplasmin (Cp) concentration and its Ox activity was established in healthy adult horses. In adult horses, serum antigenic Cp concentrations were measured by the single radial immunodiffusion (SRID) method with the affinity-purified antibody to equine plasma Cp and compared with its Ox activity. Efficient co-relation between Cp concentration and Ox activity in the sera (r = 0.93) and its Ox/Cp ratio were given. These results might contribute to the calculation of antigenic Cp concentration from its Ox activity, the analysis of holo-Cp content in serum, and the research for copper metabolism in thoroughbred horses.

Animals↗