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1.
Nature ; 620(7976): 965-970, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37648757

RESUMEN

Subjecting a physical system to extreme conditions is one of the means often used to obtain a better understanding and deeper insight into its organization and structure. In the case of the atomic nucleus, one such approach is to investigate isotopes that have very different neutron-to-proton (N/Z) ratios than in stable nuclei. Light, neutron-rich isotopes exhibit the most asymmetric N/Z ratios and those lying beyond the limits of binding, which undergo spontaneous neutron emission and exist only as very short-lived resonances (about 10-21 s), provide the most stringent tests of modern nuclear-structure theories. Here we report on the first observation of 28O and 27O through their decay into 24O and four and three neutrons, respectively. The 28O nucleus is of particular interest as, with the Z = 8 and N = 20 magic numbers1,2, it is expected in the standard shell-model picture of nuclear structure to be one of a relatively small number of so-called 'doubly magic' nuclei. Both 27O and 28O were found to exist as narrow, low-lying resonances and their decay energies are compared here to the results of sophisticated theoretical modelling, including a large-scale shell-model calculation and a newly developed statistical approach. In both cases, the underlying nuclear interactions were derived from effective field theories of quantum chromodynamics. Finally, it is shown that the cross-section for the production of 28O from a 29F beam is consistent with it not exhibiting a closed N = 20 shell structure.

3.
Phys Rev Lett ; 125(12): 122501, 2020 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-33016755

RESUMEN

We performed the first direct mass measurements of neutron-rich scandium, titanium, and vanadium isotopes around the neutron number 40 at the RIKEN RI Beam Factory using the time-of-flight magnetic-rigidity technique. The atomic mass excesses of ^{58-60}Sc, ^{60-62}Ti, and ^{62-64}V were measured for the first time. The experimental results show that the two-neutron separation energies in the vicinity of ^{62}Ti increase compared to neighboring nuclei. This shows that the masses of Ti isotopes near N=40 are affected by the Jahn-Teller effect. Therefore, a development of Jahn-Teller stabilization appears below the Cr isotopes, and the systematics in Sc, Ti, and V isotopes suggest that ^{62}Ti is located close to the peak of the Jahn-Teller effect.

4.
Phys Rev Lett ; 124(15): 152502, 2020 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-32357034

RESUMEN

Detailed spectroscopy of the neutron-unbound nucleus ^{28}F has been performed for the first time following proton/neutron removal from ^{29}Ne/^{29}F beams at energies around 230 MeV/nucleon. The invariant-mass spectra were reconstructed for both the ^{27}F^{(*)}+n and ^{26}F^{(*)}+2n coincidences and revealed a series of well-defined resonances. A near-threshold state was observed in both reactions and is identified as the ^{28}F ground state, with S_{n}(^{28}F)=-199(6) keV, while analysis of the 2n decay channel allowed a considerably improved S_{n}(^{27}F)=1620(60) keV to be deduced. Comparison with shell-model predictions and eikonal-model reaction calculations have allowed spin-parity assignments to be proposed for some of the lower-lying levels of ^{28}F. Importantly, in the case of the ground state, the reconstructed ^{27}F+n momentum distribution following neutron removal from ^{29}F indicates that it arises mainly from the 1p_{3/2} neutron intruder configuration. This demonstrates that the island of inversion around N=20 includes ^{28}F, and most probably ^{29}F, and suggests that ^{28}O is not doubly magic.

5.
Phys Rev Lett ; 124(21): 212502, 2020 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-32530645

RESUMEN

The structure of a neutron-rich ^{25}F nucleus is investigated by a quasifree (p,2p) knockout reaction at 270A MeV in inverse kinematics. The sum of spectroscopic factors of π0d_{5/2} orbital is found to be 1.0±0.3. However, the spectroscopic factor with residual ^{24}O nucleus being in the ground state is found to be only 0.36±0.13, while those in the excited state is 0.65±0.25. The result shows that the ^{24}O core of ^{25}F nucleus significantly differs from a free ^{24}O nucleus, and the core consists of ∼35% ^{24}O_{g.s.}. and ∼65% excited ^{24}O. The result may infer that the addition of the 0d_{5/2} proton considerably changes neutron structure in ^{25}F from that in ^{24}O, which could be a possible mechanism responsible for the oxygen dripline anomaly.

6.
Phys Rev Lett ; 120(17): 172501, 2018 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-29756826

RESUMEN

The (^{12}N, ^{12}C) charge-exchange reaction at 175 MeV/u was developed as a novel probe for studying the isovector spin giant monopole resonance (IVSMR), whose properties are important for better understanding the bulk properties of nuclei and asymmetric nuclear matter. This probe, now available through the production of ^{12}N as a secondary rare-isotope beam, is exothermic, is strongly absorbed at the surface of the target nucleus, and provides selectivity for spin-transfer excitations. All three properties enhance the excitation of the IVSMR compared to other, primarily light-ion, probes, which have been used to study the IVSMR thus far. The ^{90}Zr(^{12}N,^{12}C) reaction was measured and the excitation energy spectra up to about 70 MeV for both the spin-transfer and non-spin-transfer channels were deduced separately by tagging the decay by γ emission from the ^{12}C ejectile. Besides the well-known Gamow-Teller and isobaric analog transitions, a clear signature of the IVSMR was identified. By comparing with the results from light-ion reactions on the same target nucleus and theoretical predictions, the suitability of this new probe for studying the IVSMR was confirmed.

7.
Phys Rev Lett ; 121(2): 022506, 2018 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-30085708

RESUMEN

We perform the first direct mass measurements of neutron-rich calcium isotopes beyond neutron number 34 at the RIKEN Radioactive Isotope Beam Factory by using the time-of-flight magnetic-rigidity technique. The atomic mass excesses of ^{55-57}Ca are determined for the first time to be -18650(160), -13510(250), and -7370(990) keV, respectively. We examine the emergence of neutron magicity at N=34 based on the new atomic masses. The new masses provide experimental evidence for the appearance of a sizable energy gap between the neutron 2p_{1/2} and 1f_{5/2} orbitals in ^{54}Ca, comparable to the gap between the neutron 2p_{3/2} and 2p_{1/2} orbitals in ^{52}Ca. For the ^{56}Ca nucleus, an open-shell property in neutrons is suggested.

8.
Phys Rev Lett ; 120(15): 152505, 2018 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-29756883

RESUMEN

We observed the atomic 1s and 2p states of π^{-} bound to ^{121}Sn nuclei as distinct peak structures in the missing mass spectra of the ^{122}Sn(d,^{3}He) nuclear reaction. A very intense deuteron beam and a spectrometer with a large angular acceptance let us achieve a potential of discovery, which includes the capability of determining the angle-dependent cross sections with high statistics. The 2p state in a Sn nucleus was observed for the first time. The binding energies and widths of the pionic states are determined and found to be consistent with previous experimental results of other Sn isotopes. The spectrum is measured at finite reaction angles for the first time. The formation cross sections at the reaction angles between 0° and 2° are determined. The observed reaction-angle dependence of each state is reproduced by theoretical calculations. However, the quantitative comparison with our high-precision data reveals a significant discrepancy between the measured and calculated formation cross sections of the pionic 1s state.

9.
Phys Rev Lett ; 116(5): 052501, 2016 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-26894705

RESUMEN

A candidate resonant tetraneutron state is found in the missing-mass spectrum obtained in the double-charge-exchange reaction ^{4}He(^{8}He,^{8}Be) at 186 MeV/u. The energy of the state is 0.83±0.65(stat)±1.25(syst) MeV above the threshold of four-neutron decay with a significance level of 4.9σ. Utilizing the large positive Q value of the (^{8}He,^{8}Be) reaction, an almost recoilless condition of the four-neutron system was achieved so as to obtain a weakly interacting four-neutron system efficiently.

10.
J Helminthol ; 88(1): 24-31, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23137748

RESUMEN

Human alveolar echinococcosis (AE) is caused by the accidental ingestion of Echinococcus multilocularis eggs. Early detection is essential as surgical resection is the only treatment for a complete cure. However, details are unclear about changes in the antibody response during the initial stages of infection, yet such information is useful for early serodiagnosis. Therefore, a long-term investigation was performed into the time course of the antibody response before 'positive' detection. Patient sera were used for enzyme-linked immunosorbent assay (ELISA) and Western blotting (WB) analysis using crude antigens extracted from E. multilocularis protoscoleces. Rats were experimentally infected with AE and similarly analysed by ELISA and WB. Among the markers for diagnoses, the 18 kDa band (main marker) appeared last in the preoperative stages and disappeared first after operation in a WB test. Although the 18 kDa antigen can be useful as a marker for AE diagnosis, it cannot contribute to the detection of some patients before the 18 kDa band appearance. To avoid misdiagnosis, different diagnostic antigens such as the 26-28 and 7-8 kDa bands should also be considered. These bands tend to appear earlier than the 18 kDa band and thus offer the potential for early detection of AE. We first observed changes in the antibody response in a relatively early stage after infection in human AE cases. Notably, changes in the antibody response of two intermediate species were similar. These findings provide valuable information for the early detection of human AE cases in the future.


Asunto(s)
Anticuerpos Antihelmínticos/sangre , Equinococosis Hepática/inmunología , Echinococcus multilocularis/inmunología , Anciano , Animales , Antígenos Helmínticos/inmunología , Western Blotting , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Ratas , Ratas Endogámicas F344 , Factores de Tiempo
11.
Phys Rev Lett ; 108(26): 262503, 2012 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-23004971

RESUMEN

The double-differential cross sections for the (208)Pb and (90)Zr(t,(3)He) reactions at 300 MeV/u have been measured at the RI Beam Factory at RIKEN. This was the first physics experiment with the SHARAQ magnetic spectrometer. The combined analysis of the present (t,(3)He) data and previous (n,p) data provides the clearest identification for the ß(+) isovector spin monopole resonance both in the (208)Tl and (90)Y nuclei, and puts the observations of this giant resonance on a firm foundation. The measured distributions of the (t,(3)He) monopole cross sections were well reproduced by the distorted-wave Born approximation calculation, where the target transition density was calculated with the self-consistent Hartree-Fock plus random-phase approximation using the T43 Skyrme interaction. A major part of the expected ß(+) isovector spin monopole strength was found in the measured cross section spectra.

12.
Biochim Biophys Acta ; 781(1-2): 76-80, 1984 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-6696917

RESUMEN

Infectious flacherie virus is an insect picornavirus isolated from the silkworm, Bombyx mori. Its RNA was found to act as an efficient mRNA in a wheat germ extract and a rabbit reticulocyte lysate translation system. In either system the sum of molecular weights of translation products far exceeded the coding capacity of the virus genome, which suggests the occurrence of proteolytic cleavage of large primary products to smaller polypeptides as reported for other picornaviruses and/or premature termination of translation. The highest molecular weight product of 200 000 (polyprotein-like product) could be translated in both systems. One of the antigenic products common to both systems had a molecular weight of 130 000, which corresponds to the sum of molecular weights of the four major viral proteins. Another product, which comigrated with viral protein 0, the largest viral structural protein in SDS-polyacrylamide gel electrophoresis, also showed antigenicity. Peptide mapping of these polypeptides showed that the two in vitro systems translated the same cistron in the viral RNA and that the smaller polypeptide was a part of the 130 000 Da product.


Asunto(s)
Virus de Insectos/genética , Picornaviridae/genética , ARN Viral/genética , Animales , Cationes , Sistema Libre de Células , Cinética , Peso Molecular , Biosíntesis de Proteínas , Conejos , Reticulocitos , Triticum , Proteínas Virales/genética
13.
Biochim Biophys Acta ; 1088(1): 31-5, 1991 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-1846566

RESUMEN

The glpE gene of E. coli was found to be transcribed divergently with respect to glpD, which is adjacent to glpE head-to-head on the E. coli chromosome. We constructed glpD- and/or glpE-lacZ fusion plasmids, which provided glpD and lacZ as reporter genes. The expression of glpD and glpE, under the control of the cAMP-CRP complex, was examined by measuring the activities in E. coli cells of beta-galactosidase encoded by lacZ and glycerol-3-phosphate dehydrogenase encoded by glpD. In the double-reporter-gene system, the expression of glpD and glpE was found to be positively regulated by cAMP-CRP. We also confirmed that intracellular levels of the translation products and the transcripts from glpD and glpE were positively regulated by cAMP-CRP. The cAMP-mediated induction of gene expression of glpD and glpE was significantly affected by structural alterations of the single CRP-binding site between glpD and glpE. These results indicate that the single CRP-binding site is a cis-acting element involved in the positive regulation of the expression of both glpD and glpE at the transcriptional level.


Asunto(s)
Proteínas Portadoras/metabolismo , Proteína Receptora de AMP Cíclico , AMP Cíclico/metabolismo , Escherichia coli/genética , Regulación Bacteriana de la Expresión Génica , Receptores de AMP Cíclico/metabolismo , Secuencia de Bases , Cromosomas Bacterianos , Electroforesis en Gel de Agar , Escherichia coli/metabolismo , Genes Bacterianos , Datos de Secuencia Molecular , Plásmidos , Transcripción Genética
14.
Radiat Prot Dosimetry ; 165(1-4): 439-42, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25889608

RESUMEN

Many people are anxious about radiation exposure for the reason that radiation cannot be seen. With the aim of devising a way for medical personnel to perform their medical duties without worry about radiation exposure, we attempted safety management using a system that displays the air dose of radiation in real time. Measurements were made in a lung ventilation scintigraphy examination room with the use of Xe-133. An SCI-type RI detector from Hamamatsu Photonics, which displays the air dose rate in real time, was used for the measurements. These radiation measurements were continued from the start to finish of the examination. The measurements were made in two locations, on the patient inhalation tube side and on the opposite side. Measurements were made on the patient tube side in 24 tests and on the opposite side in 12 tests. The maximum air dose rate was 3.7 ± 2.1 µSv/h on the patient tube side and 1.1 ± 0.5 µSv/h on the opposite side. Thus, the level on the opposite side was about 1/5 that of the tube side. To accurately perform lung ventilation scintigraphy, a medical worker needs to observe the patient's breathing status up close. Because of this, some medical workers are worried about radiation exposure during tests. The simplest way to reduce exposure would be to maintain a distance from the examination tube that is the source of radiation. The measurements in this study were made to encourage medical workers' recognition of this fact. Displaying specific numbers not only serves as basic data for managing staff operations, but is also thought to reassure workers through visualization.


Asunto(s)
Medicina Nuclear , Salud Laboral , Dosis de Radiación , Administración de la Seguridad , Aire , Contaminantes Atmosféricos/análisis , Diseño de Equipo , Gases , Humanos , Exposición Profesional , Fotones , Monitoreo de Radiación/métodos , Protección Radiológica/métodos , Contaminantes Radiactivos/análisis , Radiometría , Cintigrafía/métodos , Radiofármacos/efectos adversos , Respiración , Riesgo , Recursos Humanos , Xenón
15.
Endocr Relat Cancer ; 11(1): 149-60, 2004 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-15027892

RESUMEN

Among inbred female cotton rats (Sigmodon hispidus) 25-50% of the animals develop spontaneous gastric carcinomas; the corresponding figure for male cotton rats is approximately 1%. Animals with carcinomas have hypergastrinaemia and gastric hypo-anacidity and the tumours are derived from enterochromaffin-like (ECL) cells. The mechanism behind the hypo-anacidity is unknown. Carcinomas are found in all female cotton rats with hypergastrinaemia lasting more than 4 months and this represents an excellent animal model for studying gastric carcinogenesis. In this study, the somatostatin analogue octreotide was given to female cotton rats to prevent carcinoma development caused by hypergastrinaemia. Twelve female cotton rats were given monthly injections of long-acting octreotide (5 mg i.m.) for 6 months. A control group of 20 animals was not given injections. Of the 20 control animals, 13 developed hypergastrinaemia and histologically invasive carcinomas or dysplasia. Of the 12 animals in the octreotide group, five developed hypergastrinaemia. None of these five animals developed histological cancer (P<0.05), whereas three had dysplasia. However, octreotide did not affect plasma gastrin concentration or antral gastrin mRNA abundance significantly. Dysplasia of the oxyntic mucosa in hypergastrinaemic animals was accompanied by a marked increase in chromogranin A-immunoreactive cells and cells positive for Sevier-Munger staining. The malignant tissue also contained groups of cells with Sevier-Munger staining. In conclusion, octreotide prevented ECL cell carcinomas in hypergastrinaemic cotton rats without lowering the gastrin concentration.


Asunto(s)
Antineoplásicos Hormonales/uso terapéutico , Carcinoma/prevención & control , Células Similares a las Enterocromafines/patología , Octreótido/uso terapéutico , Neoplasias Gástricas/prevención & control , Animales , Carcinoma/metabolismo , Carcinoma/patología , Cromogranina A , Cromograninas/metabolismo , Células Similares a las Enterocromafines/metabolismo , Femenino , Gastrinas/sangre , Gastrinas/metabolismo , Inmunoquímica , Células Parietales Gástricas/metabolismo , Células Parietales Gástricas/patología , ARN Mensajero/análisis , ARN Mensajero/metabolismo , Ratas , Sigmodontinae , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología
16.
Cancer Lett ; 57(2): 159-63, 1991 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-2025888

RESUMEN

Antitumor effect of N-1554 (alpha-dihydrodecaprenyl phosphate containing eight trans internal isoprene residues) against B16-F10 melanoma in syngeneic C57BL/6 mice was examined. B16-F10 cells were inoculated into the footpad of mice and N-1554 was intraperitoneally administered after the inoculation. The drug significantly inhibited the tumor growth in the footpad and dramatically reduced the pulmonary metastasis from the tumor. The antitumor effect of N-1554 was almost abolished when the immunosuppressant carrageenan or anti-asialo GM1 antibody was administered to mice. In addition, pretreatment of host mice with N-1554 reduced the growth of subcutaneously inoculated B16-F10 melanoma. These results suggest that enhancement of host immune system may be involved in the antitumor effect of N-1554.


Asunto(s)
Antineoplásicos , Gangliósido G(M1) , Melanoma/tratamiento farmacológico , Fosfatos de Poliisoprenilo/uso terapéutico , Animales , Anticuerpos/farmacología , Carragenina/farmacología , Línea Celular , Glicoesfingolípidos/inmunología , Neoplasias Pulmonares/prevención & control , Neoplasias Pulmonares/secundario , Masculino , Melanoma/patología , Ratones , Ratones Endogámicos C57BL , Fosfatos de Poliisoprenilo/administración & dosificación , Fosfatos de Poliisoprenilo/antagonistas & inhibidores
17.
AIDS Res Hum Retroviruses ; 11(5): 563-70, 1995 May.
Artículo en Inglés | MEDLINE | ID: mdl-7576912

RESUMEN

The V3 loop in gp120 of human immunodeficiency virus type 1 (HIV-1) is known as a principal neutralizing and cell-tropic determinant. Biotinylated synthetic V3 loop peptides derived from three different HIV-1 strains were used as ligands to identify the cell surface counterreceptor, which may participate in the infection of HIV-1. Two different cell lines, Molt-4 and U937, and three V3 loop peptides derived from LAVELI, HTLV-IIIMN, and HTLV-IIIB strains were used. The binding of HTLV-IIIB-derived peptide to the cell surface was confirmed using 125I-labeled surface proteins of both cell lines. The relative molecular mass of the major radioactive band on the autoradiogram was 32-33 kDa in both cell lines. A protein was purified from the plasma membrane fraction of Molt-4 cells using affinity columns coupled with three different V3 loop peptides. Two major polypeptides (32 and 33 kDa) were eluted from the affinity column. Size-exclusion chromatography showed that the protein migrated as a single peak with a molecular mass of 130 kDa. These proteins were separated by reversed-phase chromatography, which indicated that the 32-kDa protein is more hydrophobic than the 33-kDa protein in Molt-4 cells. A similar but not identical 130-kDa protein with 32- and 33-kDa polypeptides were also purified from U937 cells. These findings indicate that HIV-1 utilizes a tetrameric protein on the surface of Molt-4 and U937 cells on infection.


Asunto(s)
Proteína gp120 de Envoltorio del VIH/metabolismo , VIH-1/metabolismo , Fragmentos de Péptidos/metabolismo , Receptores del VIH/metabolismo , Secuencia de Aminoácidos , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD4-Positivos/virología , Cromatografía de Afinidad , Cromatografía Líquida de Alta Presión , Humanos , Datos de Secuencia Molecular , Unión Proteica , Receptores del VIH/aislamiento & purificación , Células Tumorales Cultivadas
18.
Neuroreport ; 5(8): 898-900, 1994 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-8061291

RESUMEN

Analyses of tryptophan and tyrosine metabolites in cerebrospinal fluid were performed to examine an abnormality of the monoamine neurone system in severe infantile spinal muscular atrophy (SMA type I). The levels of 5-hydroxyindoleacetic acid and homovanillic acid were significantly lower than those in controls. Decreases in the concentration of 5-hydroxyindoleacetic acid and kynurenine seemed to be related to the severity of SMA type I. These results suggest that the monoamine neurone system may play a role in the pathophysiology of SMA type I.


Asunto(s)
Monoaminas Biogénicas/líquido cefalorraquídeo , Atrofias Musculares Espinales de la Infancia/líquido cefalorraquídeo , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Triptófano/líquido cefalorraquídeo , Tirosina/líquido cefalorraquídeo
19.
Brain Res ; 837(1-2): 213-20, 1999 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-10434005

RESUMEN

Periventricular leukomalacia is an important cause of cerebral palsy and characterized by cysts and coagulation necrosis in the periventricular white matter. Since no model of periventricular leukomalacia has been established in small animals, it is expected to establish a new model of white matter injury in immature rodents. Bilateral carotid arteries were occluded in neonatal rats at 5 days of age, and the brain neuropathologically examined at 7 days of age. Among 22 brains histologically examined, 20 (90.9%) had white matter changes including coagulation necrosis and cystic lesions in and around the internal capsule, while only two had small cerebral infarction and five showed some ischemic neurons in the cerebral cortex. Cerebral blood flow (CBF) decreased to about 25% of controls in the subcortical white matter in the animals with bilateral carotid artery occlusion (BCAO). Amyloid precursor protein (APP) immunohistochemistry demonstrated various APP-immunoreactive axonal profiles in the internal capsule and the subcortical white matter, and stronger expression of APP in pyramidal neurons in the cerebral cortex of BCAO brains. These results indicated that the white matter is more vulnerable than the cerebral cortex in 5-day-old rats when CBF decreases to about 25% and suggested that this model is useful for investigating the white matter changes induced by cerebral hypoperfusion in the neonatal brain, since previous models of hypoxic-ischemic brain injury in neonatal mice and rats revealed preferential susceptibility of the gray matter. It was also indicated that APP is a sensitive marker for mild axonal disruption in the white matter of the immature brain.


Asunto(s)
Isquemia Encefálica/patología , Encéfalo/patología , Leucomalacia Periventricular/patología , Leucomalacia Periventricular/fisiopatología , Precursor de Proteína beta-Amiloide/análisis , Animales , Animales Recién Nacidos , Astrocitos/patología , Encéfalo/irrigación sanguínea , Arterias Carótidas , Corteza Cerebral/patología , Circulación Cerebrovascular , Modelos Animales de Enfermedad , Proteína Ácida Fibrilar de la Glía/análisis , Hipocampo/patología , Humanos , Recién Nacido , Leucomalacia Periventricular/metabolismo , Ratones , Neuronas/patología , Células Piramidales/patología , Ratas , Ratas Wistar , Flujo Sanguíneo Regional , Tálamo/patología
20.
Eur J Pharmacol ; 271(1): 159-66, 1994 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-7698198

RESUMEN

The antagonistic activities of compound N-3389 (endo-3,9-dimethyl-3,9- diazabicyclo[3,3,1]non-7-yl 1H-indazole-3-carboxamide dihydrochloride) at 5-HT3 and 5-HT4 receptors were examined using in vitro and in vivo assays. N-3389 showed potent 5-HT3 receptor antagonistic activities in a radioligand binding assay (pKi = 8.77), against 2-methyl-5-HT (2-Me-5-HT)-induced bradycardia in rats (ED50 = 0.73 micrograms/kg i.v., 38 micrograms/kg p.o.) and against 2-Me-5-HT-induced contraction in longitudinal muscle myenteric plexus preparations of guinea-pig ileum (IC50 = 3.2 x 10(-8) M). As a preliminary to investigating the effect of N-3389 on 5-HT4 receptors, we examined the contraction induced by 5-HT in guinea-pig ileum preparations. We confirmed that 5-HT (10(-8)-10(-5) M) induced biphasic contractions in the preparations. Furthermore, 5-HT3 receptor antagonism inhibited the late phase of the contraction induced by high concentrations of 5-HT (3 x 10(-6)-10(-5) M), whereas 5-HT4 receptor antagonism inhibited the early phase of the contraction induced by low concentrations of 5-HT (10(-8)-10(-6) M). N-3389 (10(-7)-10(-5) M) inhibited both phases of contraction induced by 5-HT. In addition, N-3389 (3 x 10(-7)-3 x 10(-6) M) was found to inhibit the increase of electrically stimulated twitch responses induced by 5-HT (10(-8) M) longitudinal muscle myenteric plexus preparation of the guinea-pig ileum. These results suggest that N-3389 acts as a 5-HT3 and 5-HT4 receptor antagonist.


Asunto(s)
Compuestos Bicíclicos Heterocíclicos con Puentes , Compuestos Bicíclicos con Puentes/farmacología , Indazoles/farmacología , Receptores de Serotonina/efectos de los fármacos , Antagonistas de la Serotonina/farmacología , Animales , Compuestos Bicíclicos con Puentes/metabolismo , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Estimulación Eléctrica , Cobayas , Frecuencia Cardíaca/efectos de los fármacos , Indazoles/metabolismo , Masculino , Plexo Mientérico/efectos de los fármacos , Ensayo de Unión Radioligante , Ratas , Ratas Wistar , Receptores de Serotonina/metabolismo , Serotonina/análogos & derivados , Serotonina/farmacología
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