Neuropharmacological assessment of potential dopamine D4 receptor-selective radioligands

Radiolabeled dopamine D4 receptor-selective agents ([3H]1-benzyl-4-[ N-(3-isopropoxy-2-pyridinyl)-N-methyl]-aminopiperidine maleate; [3 H]PNU-101958. and [125I]1-[4-iodobenzyl]-4-[ N-(3-isopropoxy-2-pyridinyl)-N-methyl]-aminopiperidine; [125I]RBI-257) were prepared and characterized. With D4.2- and D2L receptor-transfected cell membranes, [3H]PNU-101958 showed high dopamine D4 receptor affinity and selectivity, and potent inhibition by dopamine D4 receptor-selective compounds. However, its binding with rat brain homogenates showed little regional selectivity, and pharmacology inconsistent with selective dopamine D4 receptor labeling. Autoradiography indicated partial displacement of [3H]PNU-101958 by unlabeled dopamine D4 receptor ligands without regional selectivity, and lack of selective labeling with [125I]RBI-257. The results encourage further efforts to develop better dopamine D4 receptor-selective radioligands.     

Gene cloning and sequencing of BmK AS and BmK AS-1, two novel neurotoxins from the scorpion Buthus martensi Karsch.

Based on the known amino acid sequences of BmK AS and BmK AS-1, the gene specific primers were designed and synthesized for 3' and 5' RACE (Rapid Amplification of cDNA Ends). Their partial cDNA fragments obtained by 3' and 5' RACE were cloned and sequenced, and the full length cDNA sequences of BmK AS and BmK AS-1 were then completed by overlapping their two partial cDNA sequences, respectively. The predicted amino acid sequences both consist of 85 amino acid residues including a putative signal peptide of 19 residues and a mature toxin of 66 residues. They are different in 17 amino acid residues, among them 11 residues in the mature toxin. The predicted amino acid sequences of BmK AS and BmK AS-1 were almost consistent with those determined and revised (personal communication), only different in one and two residues at their COO-terminal parts, respectively. Based on the determined cDNA sequences, and using the total DNAs isolated from the scorpion venom glands as a template, the genomic DNAs of BmK AS and BmK AS-1 were also amplified by PCR and sequenced. It showed that no intron was inserted in their open reading frames, while in the exon of signal peptide sequences of other Na+, K+ and Cl- channel toxins from the same scorpion, an intron is usually found. However, the Northern blot hybridization results indicated that the sizes of their mRNA should be around 800 bp. Their extra sequences around 400 bp which might function as an intron should be located at their 5' untranslated regions.     

Molecular characterization of a new excitatory insect neurotoxin with an analgesic effect on mice from the scorpion Buthus martensi Karsch.

Besides the neurotoxins active on mammals, a new excitatory insect selective toxin with a mice analgesic activity was found and purified from the venom of the scorpion Buthus martensi Karsch (BmK) (Ji, Y.H., Mansuelle, P., Terakawa, S., Kopeyan, C., Yanaihara, N., Hsu, K., Rochat, H., 1996. Toxicon 34, 987; Luo, M.J., Xiong, Y.M., Wang, M., Wang, D.C., Chi, C.W., 1997. Toxicon 35, 723.). This peptide (designated as BmK IT-AP) is composed of 72 amino acid residues. Its primary structure was determined by automated Edman degradation of the N-terminal part of the reduced and S-carboxamidemethylated protein and its lysylendopeptidase degraded fragments. Based on the determined sequence, the gene specific primers were designed and synthesized for 3' and 5' RACE (rapid amplification of cDNA ends). Their partial cDNA fragments obtained by 3' and 5' RACEwere cloned and sequenced and the full length cDNA sequence of BmK IT-AP was then completed by overlapping their two partial cDNA sequences. It encodes a precursor of 90 amino acid residues: a signal peptide of 18 residues and a mature peptide of 72 residues which are consistent with the determined protein sequence of BmK IT-AP. The genomic DNA of the peptide was also amplified by PCR from the scorpion genomic DNA and sequenced, which is a first report on the genomic structure of a scorpion toxin specific for insects. Its sequence revealed an intron of 590 bp inserted in the end part of the signal peptide. The peptide caused a fast excitatory contraction paralysis on house fly larvae. Furthermore, the peptide also showed an obvious analgesic effect on mice, as assayed by using a twisting test model. This effect of BmK IT-AP well characterized at molecular level is first reported among the known scorpion insect neurotoxins.     

银杏提取物对培养的脑微血管内皮细胞与单核细胞和中性粒细胞 …

AIM: To study the action of Ginkgo biloba extract (GbE) on tumor necrosis factor (TNF-alpha)-induced adhesion of monocytes (Mon) and neutrophils (Neu) to cultured cerebral microvascular endothelial cells. METHODS: TNF-alpha-induced endothelial adhesivity toward Mon and Neu was studied using bovine cerebral microvascular endothelial cells (BCMEC) in vitro. The number of Mon and Neu adhering to the BCMEC monolayers was determined by flow cytometry. RESULTS: Pretreatment of BCMEC with TNF-alpha increased Mon and Neu adhesion to BCMEC from 12.5% +/- 0.2% to 31.3% +/- 0.5% and from 13.8% +/- 0.4% to 32.1% +/- 0.5%, respectively. GbE (1-100 mg.L-1) inhibited the effect of TNF-alpha in a concentration-dependent manner. E-selectin mAb (1 mg.L-1) blocked Mon and Neu adhesion to BCMEC induced by TNF-alpha. CONCLUSION: The inhibition of GbE on Mon and Neu adhesion to BCMEC was mediated through the suppression of E-selection expression.     

氟伐他汀对自发性高血压大鼠阻力血管 功能的影响

AIM: To evaluate the effects of fluvastatin, a hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitor, on the alterations of structure and function of resistant vessels in spontaneously hypertensive rats (SHR). METHODS: Eight-week-old male SHR were given fluvastatin 20 mg.kg-1.d-1 by gavage. Rats were decapitated at 16 wk. Wall-to-lumen area ratios (W/L) of thoracic aorta and mesenteric arteries (3rd grade branch) were assessed by morphometric assay. The effects of fluvastatin on vascular reactivity to sodium nitroprusside (SNP) and norepinephrine (NE), were studied with rings of thoracic aorta and mesenteric arteries isolated from rats. RESULTS: After 8 wk of treatment, histological examination showed that the wall-to-lumen area ratio was lower in SHRflu than that in SHR (0.44 +/- 0.09 vs 0.79 +/- 0.09, P < 0.05). EC50 of vasodilation response was much lower in SHRflu than that in SHR [(4.9 vs 190) pmol.L-1, P < 0.05], while EC50 of mesenteric artery rings from SHRflu was somewhat lower than that of SHR [(0.02 vs 0.04) nmol.L-1, P > 0.05]. In both aortic and mesenteric artery rings, EC50 of vasoconstriction in response to NE from SHRflu was higher than that of SHR [thoracic aorta: (0.20 vs 0.02) nmol.L-1, P < 0.05; mesentric arteries: (1.46 vs 0.72) nmol.L-1, P < 0.05]. CONCLUSION: Short-term treatment with fluvastatin ameliorated the vasomotoricity of resistant vessels, enhanced the sensitivity to vasodilator and depressed the sensitivity to vasoconstrictor; fluvastatin also attenuated the resistant vascular hypertrophy during the development of hypertension in SHR.     

槐角的避孕成分研究(Ⅱ)——化合物Ⅴ～Ⅷ的分离和鉴定

本文报道从槐角中分离到的化合物Ⅴ～Ⅷ的鉴定。经紫外、核磁共振光谱分析及物理化学常数的测定,证明化合物Ⅴ～Ⅷ分别为山萘酚-3-槐糖甙、染料木素-7-双葡萄糖甙、山萘酚-3-鼠李糖-双葡萄糖甙和染料木素-7-双葡萄糖-鼠李糖甙。这些甙水解后的甙元山萘酚和染料木素对小鼠具有抗生育活性。     

中药厚朴及其类似品的有效成分分析

本文对中药厚朴及其类似品中的有效成分——厚朴酚、和厚朴酚及木兰箭毒碱分别进行了高效液相色谱法和双波长扫描法测定;对其挥发油中化学成分进行了气-质联用分离与鉴定。     

Copolymerization of propene with 1-alkenes using a MgCl2/TiCl4 catalyst

Copolymerization of propylene

1 System name: propene.

and 1-alkenes (1-octene, 1-decene, 1-dodecene, 1-tetradecene, 1-hexadecene) were studied with the catalyst system MgCl₂/TiCl₄-Al(i-Bu)₃. It was found that the polymerization productivity and the consumption rate of propylene are improved significantly in the presence of the comonomer. The total productivity of propylene/1-alkene copolymerizations decreases as follows: 1-octene > 1-decene > 1-dodecene > 1-hexadecene > 1-tetradecene. The reactivity ratios were estimated from the copolymerization results.     

Replantation of frozen and boiled autogenous mandible

Mandibles devitalized by freezing or boiling after being removed from animals were reimplanted to evaluate their potentials of reunion and growth with X-ray and histological methods. The results suggested that the osteo-induction may play a partial role in the bone healing of frozen bone graft besides "creeping substitution", while the boiled one only provided a scaffold into and around which bone formation can occur. According to the rate and degree of bone graft repair, the frozen was better than the boiled which was resorbed and replaced at a slower rate.