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21.
To clarify the role of endogenous histamine in learning and memory, the effect of -fluoromethylhistidine on active avoidance response in rats was studied. -Fluoromethylhistidine (20–100 mg/kg or 10–50 µg) significantly (P<0.05 orP<0.01) prolonged the response latency in active avoidance response when administered by either intraperitoneal or intracerebroventricular injection. These effects were dose-related and long lasting. A prolongation of the response latency induced by an intraperitoneal injection of -fluoromethylhistidine (100 mg/kg) was antagonized by intracerebroventricular injection of histamine (10 and 20 ng) in a dose-dependent manner. In addition, the acquisition of this response was retarded by a consecutive intracerebroventricular injection of -fluoromethylhistidine (50 µg), whereas histamine (100 ng) facilitated the response acquisition when administered by the same route. Both intraperitoneal (100 mg/kg) and intracerebroventricular injection of -fluoromethylhistidine (50 µg) significantly (P<0.05 orP<0.01) decreased the brain histamine content, especially in the hippocampus and hypothalamus. When -fluoromethylhistidine (50 µg) was injected intracerebroventricularly, there is a high correlation between a prolongation of the response latency and a decrease in histamine content of these brain areas. Based on these findings, it was concluded that an intimate relation may exist between a prolongation of response latency in the active avoidance response and a decrease in the brain histamine content; endogenous histamine may play an important role in learning and memory recollection in rats. 相似文献
22.
John E. Schurig William C. Rose Hideo Kamei Yuji Nishiyama William T. Bradner Dale A. Stringfellow 《Investigational new drugs》1990,8(1):7-15
Summary BMY-28175 is a novel antitumor antibiotic produced in fermentation by Actinomadura verrucosospora. The cytotoxic effects of BMY-28175 were determined using murine and human tumor cell lines in vitro. Following 72 hour exposure, the drug had IC50 values 1.5 to 13.5 ng/ml in a microtiter assay. BMY-28175 was evaluated for antitumor activity against several experimental murine and human tumor models. The drug administered ip was active against ip implanted P388 leukemia, L1210 leukemia, B16 melanoma, M109 lung carcinoma, C26 colon carcinoma, M5076 sarcoma and Lewis lung carcinoma. In addition, BMY-28175 administered iv was active against iv implanted P388 and L1210 leukemias. BMY-28175 was active against sc implanted B16 melanoma (increased lifespan and/or inhibition of primary tumor growth) in about 60% of the tests. The growth of sc implanted M109 was inhibited by BMY-28175 in a single experiment. BMY-28175 was also active against the MX-1 human mammary xenograft implanted in the subrenal capsule of nude mice. The optimal dose for BMY-28175 in these various studies ranged from 0.16 g/kg per injection with consecutive daily (qd1-9) administration, to 51.2 g/kg with single dose administration. The results of these studies indicate that BMY-28175 is one of the most potent antitumor agents yet observed, with a broad spectrum of activity against tumors of murine and human origin and activity against tumors located distal to the site of drug administration. 相似文献
23.
Kamei H Hashimoto Y Koide T Kojima T Hasegawa M Umeda T 《Cancer biotherapy & radiopharmaceuticals》1997,12(5):341-344
Melanoidin, which belongs to the melanin group of molecules, was extracted from the polysaccharide biological response modifier PSK. Melanoidin was cultured together with HCT-15 cells derived from human colon cancer and with AGS cells derived from human gastric carcinoma. After four days of culture, cell count was compared with that of the control cells. Significant suppression was observed, that is, 50% suppression was shown at concentrations of melanoidin between 200 and 100 micrograms/ml. A histogram generated by flow cytometry showed elevation of the tetraploid peak and of that between diploid and tetraploid peaks, suggesting blockage of S phase and G2 to M phase of the cell cycle. Thus, melanoidins contained in the immunomodulator PSK revealed to have a direct tumor cell growth inhibitory effect. 相似文献
24.
Saeki Toshiaki; Salomon David S.; Johnson Gibbes R.; Gullick Willium J.; Mandai Koichi; Yamagam Keitaro; Moriwaki Shosuke; Tanada Minoru; Takashima Shigemitsu; Tahara Eiichi 《Japanese journal of clinical oncology》1995,25(6):240-249
The frequency of expression and localization of cripto-1 (CR-1),amphiregulin (AR), transforming growth factor alpha (TGF), epidermalgrowth factor receptor (EGFR) and erbB-2 were examined by immunohistochemistryin 45 carcinomas and adjacent non-involved normal colon mucosa.Thirty (66.7%), 24 (53.3%), 23 (51.1%), 23 (51.1%) and 13 (28.9%)of the 45 carcinomas showed positive staining for CR-1, AR,TGF, EGFR and erbB-2, respectively, whereas 7 (15.5%), 17 (37.7%),15 (33.3%), 20 (44.4%) and 0 (0%) of the corresponding non-involvednormal mucosa specimens were reactive. Among 13 carcinomas withlymph node involvement, 10 (76.9%), 8 (61.5%), 10 (76.9%), 8(61.5%) and 7 (53.8%) exhibited positive staining for CR-1,AR, TGF-, EGFR and erbB-2, respectively. There was a statisticallysignificant association between the frequency of either TGF(P<0.05) or erbB-2 (P<0.05) expression and lymph nodemetastasis. In addition, a signficantly higher frequency ofpositive staining for TGF was observedin Dukes' grade C carcinomas(P<0.05). Finally, significant trends for coexpression ofEGFR and either TGF (P<0.01) or AR (P<0.05) were detectedin carcinomas. These data suggest that AR and TGF may play animportant role in the development of colorectal carcinomas throughan autocrine mechanism involving EGFR, and demonstrate thatTGF and erbB-2 may be more reliable indicators of metastasisor prognosis than CR-1, AR or EGFR in human colon cancers. 相似文献
25.
Kamei J Kashiwazaki T Taki K Hitosugi H Nagase H 《European journal of pharmacology》1999,369(3):319-323
The duration of the somatostatin-, bradykinin- or prostaglandin F2alpha-induced nociceptive response was significantly less in diabetic mice than in non-diabetic mice. Subcutaneous injection of 7-benzylidenenaltrexone (0.1, 0.3 and 1 mg/kg), an antagonist of delta1-opioid receptors, had no significant effect on either somatostatin-, bradykinin- or prostaglandin F2alpha-induced nociceptive responses in non-diabetic mice. 7-Benzylidenenaltrexone (0.1 and 0.3 mg/kg, s.c.) also had no significant effect on somatostatin- or prostaglandin F2alpha-induced nociceptive responses in diabetic mice. However, the bradykinin-induced nociceptive response in diabetic mice was dose-dependently and significantly increased when 7-benzylidenenaltrexone (0.1, 0.3 and 1 mg/kg, s.c.) was injected 10 min before the injection of bradykinin. These results suggest that a spinal delta1-opioid receptor-mediated endogenous antinociceptive system may inhibit the bradykinin-mediated nociceptive responses in the second phase of the formalin-induced nociceptive response in diabetic mice. 相似文献
26.
We examined the tail-flick response to various heat intensities in diabetic and non-diabetic mice. Heat intensities were set to one of five values by adjusting the source voltage of a 50-W projection bulb to 25, 35, 50, 65 and 80 V. These heat intensities produced surface skin heating rates of 0.1, 0.4, 0.9, 3.0 and 7.3 degrees C/s, respectively. Tail-flick latencies at source voltages of 35 and 50 V in diabetic mice were significantly shorter than those in non-diabetic mice. However, there were no significant differences in tail-flick latencies at 25, 65 and 80 V. In non-diabetic mice, tail-flick latencies were not affected by intrathecal (i.t.) pretreatment with capsaicin 24 h before testing. Tail-flick latencies at 35 and 50 V in diabetic mice were increased by pretreatment with capsaicin. Moreover, although tail-flick latencies in non-diabetic mice were not affected by i.t. pretreatment with calphostin C, a selective protein kinase C inhibitor, those at 35 and 50 V in diabetic mice were increased. However, i.t. pretreatment with (8R, 9S, 11S)-(-)-9-hydroxy-9-n-hexyloxy-carbonyl-8-methyl-2, 3, 9, 10-tetrahydro-8, 11-epoxy-1H, 8H, 11H-2, 7b, 11a-triazadibenzo [a, g]cycloocta[cde]-trinden-1-one (KT5720), a selective protein kinase A inhibitor, did not affect tail-flick latencies in either diabetic or non-diabetic mice. In non-diabetic mice, i.t. pretreatment with phorbol 12,13-dibutyrate (PDB), a protein kinase C activator, decreased tail-flick latencies at 35 and 50 V. Tail-flick latencies in diabetic mice were not affected by i.t. pretreatment with PDB 60 min before testing. Furthermore, the attenuation of tail-flick latencies induced by i.t. pretreatment with PDB in non-diabetic mice was reversed by i.t. pretreatment with capsaicin 24 h before testing. These results indicate that diabetic mice exhibit thermal allodynia and hyperalgesia. Furthermore, this thermal allodynia and hyperalgesia in diabetic mice may be due to the enhanced release of substance P followed by activation of protein kinase C in the spinal cord. 相似文献
27.
Kamei J Ohsawa M Suzuki T Saitoh A Endoh T Narita M Tseng LF Nagase H 《European journal of pharmacology》1999,383(3):241-247
To clarify the pharmacological properties of (+)2-Methyl-4aalpha-(3-hydroxyphenyl)-1, 2, 3, 4, 4a, 5, 12, 12aalpha-octahydro-quinolino[2, 3, 3-g]isoquinoline ((+)-TAN-67), the effect of (+)-TAN-67 on the antinociception induced by the intrathecal (i.t.) administration of nociceptin/orphanin FQ was studied in mice using the tail-flick test and the formalin test. I.t. administration of (+)-TAN-67, at doses of 1 to 10 ng, facilitated the tail-flick response in a dose-dependent manner in mice. In addition, i.t. administration of (+)-TAN-67 (1 to 10 ng) in mice produced a marked pain-like aversive responses. I.t. pretreatment with D-Pro(9)-[spiro-gamma-lactam]-Leu(10)-Trp(11)-physalaemin(1-11) (GR82334, 0.1-1.0 nmol), a potent and selective tachykinin NK(1) receptor antagonist, dose-dependently blocked the reduction of the tail-flick response induced by (+)-TAN-67. Furthermore, (+)-TAN-67-induced facilitation of the tail-flick response was abolished in capsaicin-treated mice. On the other hand, (+)-TAN-67-induced flinching responses were dose-dependently and significantly reduced by i.t. pretreatment with GR82334 (0.1-1.0 nmol). The duration of i.t. (+)-TAN-67-induced flinching responses was significantly reduced in capsaicin-treated mice as compared with naive mice. I.t. administration of nociceptin/orphanin FQ (1-10 nmol) dose-dependently increased the tail-flick latency. I.t. administration of nociceptin/orphanin FQ (0.1-1.0 nmol) significantly and dose-dependently reduced the first-phase nociceptive response, but not the second-phase nociceptive response. I.t. pretreatment with (+)-TAN-67 (0.3-3.0 microg) for 30 min dose-dependently attenuated the antinociception induced by i.t. nociceptin (10 nmol) in the tail-flick test. Furthermore, the antinociceptive effect of nociceptin/orphanin FQ (1 nmol, i.t.) on the first-phase response in the formalin test was dose-dependently attenuated by s.c. pretreatment with (+)-TAN-67 (0.3-3.0 microg). (+)-TAN-67 (0.3-3.0 microg, i.t.), by itself, did not facilitate the tail-flick response or produce apparent behavioral changes. It is possible that (+)-TAN-67 has an antagonistic effect on nociceptin/orphanin FQ-induced antinociception. 相似文献
28.
Heme-dependent radical generation: possible involvement in antimalarial action of non-peroxide microbial metabolites, nanaomycin A and radicicol 总被引:1,自引:0,他引:1
Antimalarial screening was performed for microbial metabolites that simulate artemisinin in their mode of action, a potent antimalarial component of an herbal remedy with a characteristic peroxide structure. Nanaomycin A was identified in this screen as an antimalarial compound, together with radicicol and several other compounds already reported (J. Antibiotics 51: 153 approximately 160, 1998). Nanaomycin A inhibited in vitro growth of the human malaria parasite Plasmodium falciparum with an IC80 value of 33.1 nM. It was as potent as radicicol and about 1/10 as potent as artemisinin. Studies on the mode of action suggested that the antimalarial action of the two non-peroxides, nanaomycin A and radicicol, involved heme-dependent radical generation, as is for the peroxide artemisinin. Namely, the inhibition of in vitro growth of malaria parasite by nanaomycin A or radicicol was reversed by tocopherol, a radical scavenger added to the assay mixture. Secondly, in a reaction system established for radical detection, in which a test radical donor and beta-alanylhistidine as a radical recipient were incubated with and without hemin, the two compounds caused heme-dependent decreases of beta-alanylhistidine, as did artemisinin. Among the 14 microbial metabolites identified during this screening, a correlation was observed between antimalarial activity and heme-dependent radical generating activity. 相似文献
29.
Kamei H Koide T Kojima T Hashimoto Y Hasegawa M 《Cancer biotherapy & radiopharmaceuticals》1998,13(3):185-188
Quinones were studied for their growth inhibitory effect on cultured malignant cells. HCT-15 cells derived from human colon carcinoma were used for these experiments. Quinones used were arbutin in the benzoquinone group, juglone and lawsone in the naphthaquinone group, alizarin, emodin, 1,8-dihydroxyanthraquinone, and anthraquinone in the anthraquinone group, and xanthone. Cultured cells were incubated with various concentrations of the quinones for four days in a 5% CO2 incubator, after which cell numbers were counted and significance of differences was analyzed by Student's t test. Anthraquinones and naphthaquinones used in these experiments were more effective than the monocyclic quinone. The 50% suppression dose was less than 12.5 micrograms/ml for them. The number of OH groups seemed to play an important role in the degree of the cell growth inhibition: anthraquinones with 2 or 3 OH groups were more effective than those with no OH group like, 9,10-dioxoanthracene and xanthone. In fact, anthraquinones with no OH group and xanthone were not significantly effective. Flow cytometric histograms revealed a specific pattern; that is, lawsone and juglone in the naphthaquinone group and alizarin and 1,8-dihydroxy-anthraquinone in the anthraquinone group blocked mainly the S phase, and emodin in the anthraquinone group blocked the G1 to S phase of the cell cycle. 相似文献
30.
T Yamasaki Y Narita H Hoshi S Aburaki H Kamei T Naito H Kawaguchi 《The Journal of antibiotics》1991,44(6):646-658
The synthesis and biological properties of 1-N-[4-(substituted)amidino and guanidino-2-hydroxybutyryl]kanamycins A and B are described. Reaction of 3,3",6'-tri-N-tert-butoxycarbonyl-amikacin with an appropriate amidinating or guanidinating reagent and subsequent deblocking gave a series of amikacin derivatives having an amidino or guanidino group on the 4"'-position. The corresponding kanamycin B analogs were also prepared by a similar procedure. Among these derivatives, 1-N-(4-formamidino- and guanidino-2-hydroxybutyryl)kanamycins A (7a and 7k) and B (11 and 14) exhibited antibacterial activity similar to the corresponding 4-amino analogs. The nephrotoxic potential of selected compounds is also briefly discussed. 相似文献