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71.
Yuki Kanase Takafumi Kitada Hidetsugu Tabata Kosho Makino Tetsuta Oshitari Hiromi Ohashi Takashi Yoshinaga Hideaki Natsugari Hideyo Takahashi 《Bioorganic & medicinal chemistry》2018,26(9):2508-2513
The physicochemical properties of 4-substituted carbamazepine derivatives were investigated. It was elucidated that the 4-substitution is not effective in reducing the rotations (E/Z) about the N—C1′ axes around the outer carbamoyl moiety. However, the atropisomers were isolated with high stereochemical stability, meaning that the 4-substitution reduced the butterfly motion of the tricyclic ring system efficiently. The Cl/CH3-substituted carbamazepine derivatives showed greater inhibitory effects on hNav1.2 channel currents compared with carbamazepine, although no difference in the activity between enantiomers was observed. 相似文献
72.
M. Nakai Kiyotaka Toshimori Kazuya Yoshinaga Tetsuo Nasu Rex A. Hess 《Cell and tissue research》1998,294(1):145-152
Effects of a single, high dose of orally administered carbendazim (100 mg/kg) on acrosome formation in the early phases of
spermiogenesis were examined by electron microscopy and immunocytochemistry up to day 7.5 post-treatment. No obvious abnormality
of acrosome development was noted in the Golgi phase spermatids on day 1.5 post-treatment. On day 3, step 1 spermatids were
seen in stage III seminiferous tubules. In stage V tubules at this post-treatment interval, direct connections between the
trans-side saccules of the Golgi stacks and the outer acrosomic membranes were observed in step 5 spermatids. Similar direct
connections between these two organelles were also observed in the advanced round spermatids in later stages at days 4.5 and
7.5. On day 4.5, step 1 and 3 spermatids were seen in stage V tubules. On day 7.5, round spermatids with various abnormalities
of acrosome development were observed in stage VII tubules, in addition to the discontinuous and granular acrosomes reported
previously. These features were not observed in testes of control animals. In the immunocytochemical analysis using an antibody
mMN7 that recognizes a protein delivered from the Golgi apparatus to the acrosome, spermatids exposed to carbendazim showed
various abnormal immunostaining patterns in the acrosomes. On the other hand, strong immunoreactivity was observed in the
Golgi saccules connecting to the acrosomes. These results suggest that in testis treated with carbendazim acrosome development
is impaired during the early phases of spermiogenesis, and material supply from the Golgi apparatus to the acrosome is perturbed,
which is a possible cause of the abnormal development.
Received: 31 March 1998 / Accepted: 28 May 1998 相似文献
73.
Glutathione transferases (GSTs) are multifunctional enzymes found in many organisms. We recently identified vanadium-binding GSTs, designated AsGSTs, from the vanadium-rich ascidian, Ascidia sydneiensis samea. In this study, the metal-selectivity of AsGST-I was investigated. Immobilized metal ion affinity chromatography (IMAC) analysis revealed that AsGST-I binds to V(IV), Fe(III), and Cu(II) with high affinity in the following order Cu(II)>V(IV)>Fe(III), and to Co(II), Ni(II), and Zn(II) with low affinity. The GST activity of AsGST-I was inhibited dose-dependently by not V(IV) but Cu(II). A competition experiment demonstrated that the binding of V(IV) to AsGST-I was not inhibited by Cu(II). These results suggest that AsGST-I has high V(IV)-selectivity, which can confer the specific vanadium accumulation of ascidians. Because there are few reports on the metal-binding ability of GSTs, we performed the same analysis on SjGST (GST from the schistosome, Schistosoma japonicum). SjGST also demonstrated metal-binding ability although the binding pattern differed from that of AsGST-I. The GST activity of SjGST was inhibited by Cu(II) only, as that of AsGST-I. Our results indicate a possibility that metal-binding abilities of GSTs are conserved among organisms, at least animals, which is suggestive of a new role for these enzymes in metal homeostasis or detoxification. 相似文献
74.
In cardiac myocytes, the effect of alpha1-adrenergic stimulation on L-type Ca current remains to be clarified. We examined this issue by the transient coexpression of alpha1-adrenoceptors on BHKC12 cells, where recombinant Ca channels composed of cardiac alpha1 subunit and skeletal beta, gamma, alpha2/delta subunits were stably expressed. After transfection of plasmid DNA encoding bovine alpha1C-adrenoceptors, bath-applied phenylephrine potentiated the cloned Ca channel current during perforated-patch whole-cell recording by 26+/-6% in 6 out of 12 cells. The potentiation was elicited also by methoxamine, and was blocked by prazosin. Phenylephrine also increased the channel open probability during cell-attached single channel recording in 7 out of 15 cells. The ratio of successful modulation of Ca channels was in accordance with the ratio of successful expression of alpha1-adrenoceptors, as estimated by beta-galactosidase staining. These results suggest that the stimulation of alpha1C-adrenoceptors is linked to potentiation of cardiac L-type Ca current. BHK cells provide a valuable expression system to study the modulation of Ca channels evoked by a receptor stimulation. 相似文献
75.
76.
Hidefumi Yoshinaga Shuji Masumoto Koji Koyama Naoya Kinomura Yuji Matsumoto Taro Kato Satoko Baba Kenji Matsumoto Tomoko Horisawa Hitomi Oki Kazuki Yabuuchi Toru Kodo 《Bioorganic & medicinal chemistry》2017,25(1):293-304
We report the discovery of a novel benzylpiperidine derivative with serotonin transporter (SERT) inhibitory activity and 5-HT1A receptor weak partial agonistic activity showing the antidepressant-like effect. The 3-methoxyphenyl group and the phenethyl group of compound 1, which has weak SERT binding activity, but potent 5-HT1A binding activity, were optimized, leading to compound 35 with potent and balanced dual SERT and 5-HT1A binding activity, but also potent CYP2D6 inhibitory activity. Replacement of the methoxy group in the left part of compound 35 with a larger alkoxy group, such as ethoxy, isopropoxy or methoxy-ethoxy group ameliorated CYP2D6 inhibition, giving SMP-304 as a candidate. SMP-304 with serotonin uptake inhibitory activity and 5-HT1A weak partial agonistic activity, which could work as a 5-HT1A antagonist, displayed faster onset of antidepressant-like effect than a representative SSRI paroxetine in an animal model. 相似文献
77.
Yoshinaga K 《Seminars in cell & developmental biology》2008,19(2):161-169
Pituitary and ovarian hormones prepare the endometrium for successful blastocyst implantation and support its process directly or indirectly through the action of growth factors, cytokines and other molecules. Many of the blastocyst implantation essential factors (BIEFs) are modulators of the maternal immune system. Since little is known as to the action of these molecules on the uterine lymphocytes, its clarification is imperative to the understanding of the process of blastocyst implantation. 相似文献
78.
Proper identification of Anisakis species infecting host fishes is very important to both human health and fish disease diagnosis. The foremost problem in the identification of Anisakis larvae in fishes is that L3 larvae cannot be easily differentiated morphologically, especially between A. simplex (sensu stricto) (s.s.) (Rudolphi, 1809) and A. pegreffii Campana-Rouget et Biocca, 1955. Instead, molecular means such as allozyme, mitochondrial DNA (mtDNA) cox2 region and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analyses had been successfully used. In this study, morphological differences of L3 larvae collected from fishes and in vitro-cultured L4 larvae and adult A. simplex (s.s.) and A. pegreffii were evaluated. Anisakis larvae were collected from 7 different host fishes within Japan. Undamaged A. simplex (s.s.) and A. pegreffii collected from Oncorhynchus keta (Walbaum) and Scomber japonicus Houttuyn, respectively, were used for in vitro-culture in order to obtain L4 and adult stages. Species identification was confirmed by PCR-RFLP analysis of the ITS region (ITS1-5.8S-ITS2) of ribosomal DNA and by mtDNA cox2 gene sequencing. Results revealed that L3, L4 and adult stages of A. simplex (s.s.) and A. pegreffii are morphologically distinguishable based on ventriculus length, wherein the former has longer ventriculus (0.90–1.50 mm) than the latter (0.50–0.78 mm). For oesophagus/ventriculus ratio, these two species are distinguishable only during L4 and adult stages. Also, adult male A. simplex (s.s.) and A. pegreffii were found to be distinguishable by differences in the distribution pattern of the caudal papillae, particularly the 3rd pair of distal papillae. 相似文献
79.
80.