阿片受点不可逆部分激剂A-α-CAO的药理研究

A-α-CAO对小鼠(icv)具有弱而短暂的镇痛作用并能拮抗吗啡(Mor)镇痛效应3—4d。未见A-α-CAO有成瘾倾向。小鼠输精管(MVD)试验表明A-α-CAO为阿片受点部分激剂,Ke为9×10~(-9)mol/L。保温时间较长或剂量较大,其拮抗效应经多次冲洗仍然存在,激剂作用亦不能被纳洛酮(N_x)翻转。A-α-CAO对豚鼠回肠纵肌(GPI)呈完全激剂效应,IC_(50)为5.7×10~(-10)mol/L,冲洗不能除去此种作用,但可被N_x翻转。在大鼠输精管(RVD)和兔输精管(RbVD)上A-α-CAO呈抗剂效应,pA_2值分别为7.5和7.6,作用也不易被冲洗除去。A-α-CAO可抑制~3H-依托啡(~3H-Etor)与小鼠脑勻浆P_2制备的特异给合,IC_(50)为3.2×10~(-9)mol/L,冲洗6次后A-α-CAO对~3H-Etor高亲合力结合的抑制仍达96％。     

PARADOXICAL EFFECT OF A GnRH AGONIST ON STEROIDOGENESIS IN CULTURED MONKEY GRANULOSA CELLS

In this study we demonstrate: (i) The GnRH agonist exerts a direct dose-dependet stimulative effect on the aromatase activity and progesterone production in cultured monkey granulosa cells; (ii)the stimulative effect on steroidogenesis can be completely blocked by concomitant treatment with a GnRH antagonist, suggesting that the actions of GnRH are mediated through stringent stereospecific recongnition sites; (iii) in addition to the stimulative effect, the GnRH agonist in the presence of gonadotropins also exerts an inhibitory effect, even though the peptide by itself is more effective in the stimulation of steroidogenesis, and the stimulation of gonadotropin on steroidogenesis could be gradually restored by decreasing the concentration of the GnRH agonist in the culture; and (iv) paradoxical effect can also be observed in the presence of cAMP-inducing agents, suggesting that the inhibitory action of the peptide on gonadotropin-induced steroidogenesis is localized at a step distal to the stringent reco     

Yuanhuacin A Is a Selective Antagonist of Phorbol Ester Receptor in Protein Kinase C

Protein kinase C with a molecular weight of 82 kD has been purified to electrophoresis homogenous from rat brain through a series of chromatography columns including DE-52, Sepharose G-200 and phenyl-Sepharose. The enzyme possessed autophosphorylation activity. Yuanhuacin A inhibited the ~3H-phorbol-12, 13-dibutyrate (~3H-PdBu) binding of PKC with an IC_(50) value of 1.48±0.28×10~(-8) mol/L when the concentration of ~3H-PdBu was 1.5×10~(-9) mol/L (K_i=1.2×10~(-8) mol/L). Yuanhuacin A inhibited the PdBu-stimulated PKC activity in the catalysis of the phosphorylation of Histone Ⅲ-S with an IC_(50) of 2.82±0.37×10~(-9) mol/L (PdBu=10~(-6) mol/L), while it had no effect on the basal and Ca~(2+)-stimulated PKC activity in the same assay system. This result suggests that Yuanhuacin A is a selective antagonist of the phorbol ester receptor in protein kinase C.     

THE BIPHASIC EFFECTS OF SOME OPIATES AND OPIOID PEPTIDES ON RAT VAS DEFERENS

It has been found that the effects of opiates and opioid peptides on RVD are of two types. Compounds of the first type such as Etor, Eton, fentanyl and prodinc derivatives, Met-and Leu-Enk and DADL are biphasic in nature. At lower concentrations (10~(-8)-10~(-5)M) they have inhibitory effects and at higher concentrations (10~(-5)-10~(-4)M) they are excitatory. Compounds of the second type, such as Mor, benzomorphan derivatives, Cyc and SKF and the antagonist Nx have virtually no or only weakly inhibitory effects but may antagonize the inhibitory effect produced by the first group of compounds at lower concontrations. MC belongs to the second type, but it cannot antagonize the inhibitory effect of β-End. The results are discussed in terms of multiple receptors, the high and low affinity binding sites, and the interrelationship between receptors.     

TETRAHYDROPROTOBERBERINE—A NEW CHEMICAL TYPE OF ANTAGONIST OF DOPAMINE RECEPTORS

In rats lesioned by unilateral micro-injection of 6-OHDA into substantia nigra, the apomorphine-induced contralateral rotation and the amphetamine-induced ipsilateral rotation were antagonized by THB, l-THP and haloperidol. Scopolamine reversed the antagonistic effect of THB against amphetamine. Thus, THB and 1-THP exhibited the DA-receptor antagonistic property which was similar to that of haloperidol.l-SPD (10mg/kg), however, only antagonized the amphetamine-challenged rotational response, while it could not antagonize, but potentiate, the apomorphine-challenged rotational response. So, l-SPD might be a partial agonistie antagonist of DA-receptors, and its effect was more potent than that of THB and l-THP. l-SPD would be ascertained further in clinic trial.From these results and others, the authors suggest that THPB is a new chemical type of antagonist of brain DA-receptors.     

The Antagonistic Effect of Cholecystokinin Octapeptide (CCK-8) on Opioid Effects in Cardiovascular Activities Was Mediated by CCK-B Receptor

Previous studies have shown that CCK-8 has distinct antiopioid effect in the central sites related with pain control and blood pressure control. The aim of this study was to explore the receptor mechanism by which CCK-8 antagonized the depressor effect of u- and k-opioid(?) agonists, and to observe whether CCK-8 could antagonize the depressor effect induced by muscimol, a nonopioid substance. The results showed that (i) The antagonistic effect of CCK-8 on opioid-induced hypotension could be blocked by intrathecal (i.t.) administration of CCK-B antagonist L-365, 260 at nanogram doses, or by CCK-A antagonist devazepide at doses 20—40 times higher than L-365, 260, indicating that it was the CCK-B receptor which mediates the antiopioid effect. (ⅱ) The depressor effect induced by intrathecal muscimol, a GABA agonist, was blocked neither by naloxone nor by CCK-8, supporting the notion that CCK-8 is an endogenous opioid antagonist rather than a universal anti-hypotension agent.     

MECHANISM OF INTERFERON ACTION Ⅹ——ANTAGONISTIC EFFECT OF ATP ON pppA2''''p5''''A2''''p5''''A RECEPTOR

pppA2'p5'A2'p5'A (2'-5'P_3A_3) receptor may be the first one in the oligonucleotide field.But ATP can compete with 2'-5'P_3A_3 for the receptor. This raises a question whether this is anATP receptor. If not, what is the role of ATP for this receptor? Data available in this arti-cle show that ATP can bind to macrophages with saturability and reversibility. So ATPappears to be also a ligand of the receptor for 2'-5'P_2A_3. But the binding of ATP did notdevelop phagocytic effect as mentioned before~([11]). Moreover, ATP inhibited the enhancementof phagocytosis of macrophages by 2'-5'P_3A_3 when it acted together with 2'-5'P_3A_3 on mac-rophages at the same time. It is concluded that ATP is an antagonist of 2'-5'P_3A_3 receptor.When macrophages were treated with ATP prior to 2'-5'P_3A_3 and the binding sites for 2'-5'P_3A_3P were first occupied by ATP, both the binding ability and the biological effect of2'-5'P_3A_3 were all markedly blocked. The above data convincingly show that the action of2'-5'P_3A_3 is     

THE EFFECT OF HOT DRAWN ON THE PHYSICAL AGING OF ATACTIC POLYSTYRENE

The physical aging behavior of atactic polystyrene (aPS) films achievedunder different drawing conditions has been studied by optical birefringence and modulatedifferential scanning calorimeter (m.d.s.c.). The results show that on annealing at specifictemperature below glass transition temperatue (T_g), the enthalpy relaxation (△H) and T_gdecrease with increasing of birefringence (△n). On the other hand, the effect of moleculardraw ratio (MDR) is confusing: △H and T_g decrease with increasing of MDR in the earlystage of aging, but the MDR's effect become unobvious with the development of aging.It may be concluded that the ordered domain generated by the drawing below or aboveglass transition temperature will affect the development of physical aging behavior. Theviewpoint of cohesional entanglement is used to account for the above observations.     

DIFFERENT EFFECTS OF ENANTIOMERS OF TETRAHYDROPALMATINE ON DOPAMINERGIC SYSTEM

Tetrahydropalmatine (THP) has two enantiomers with different effects on the brain dopaminergic system. Using [~3H]spiperone for DA receptor binding assay, it was found that l-THP had an affinity to DA receptors (K_1=0.2μM). Neither d-THP nor reserpine showed such an effect even at concentrations higher than 100 or 1000μM. Based on the fact that the presynaptic DA receptors take part in feed-back regulation on tyrosiue hydroxylase activity, DOPA accumulation could be observed in rat striatum after injection of benserazide. A small dose of l-THP (2.5, 5, 10 mg/kg, ip.) caused an elevation of DOPA level by 49—282% versus the control value, and could reverse the decrease of DOPA level induced by apomorphine, a DA receptor agonist. On the contrary, d-THP displayed a biphasic effect on DOPA level, slight decrement (26—37%) at 10 and 25mg/kg, naught at 50mg/kg, and a 91% increment at 100 mk/kg, which was less than that of l-THP at 5mg/kg. Moreover, measured by pulse voltammetry, DOPAC level in the striatum     

A molecularly imprinted polymer receptor for the enantiomeric recognition of amino acid hydantoins mimicking cooperative hydrogen bonds between nucleotide bases

Using acrylamide as hydrogen bonding functional monomer and (5R)-5-benzylhydantoin as template, a molecularly imprinted polymer was prepared in a polar solvent, which exhibited good enantiomeric recognition properties. The binding characteristics and selectivity of the polymer were evaluated by batch methods. Scatchard analysis showed that two classes of binding sites were produced in the polymer matrix and their dissociation constants were calculated to be 3.5 × 10-5mol/L and 4.3 ×10-4 mol/L, respectively, by utilizing the model of multiple independent classes of binding sites. These results were more reasonable than those obtained by Scatchard analysis , which was in agreement with the prediction of the binding characteristics of the polymer by exploring the effect of acrylamide on UV spectra of (5R)-5-benzylhydantoin. The substrate- and enantio-selectivity of the polymer was investigated. Finally, the study of effect of water on the chiral separation factor of the polymer further proved that the hy     

LOADING CORRECTION OF OCEANIC TIDES IN THE MAINLAND OF CHINA

The response of radial inhomogeneous elastic earth under the action of oceanic tides is studied by use of the combination of convolution integral with spherical harmonic expansion. In the meantime, the effect of oceanic tides on gravity, tilt and strain in the mainland of China is estimated, and the accuracy of loading correction is also briefly analysed. Results show that the loading effect along the coast of China cannot be neglected, for gravity it is about 5％ of body tides, for tilt it reaches the same magnitude as body tides, for strain about 50％. The result obtained can be used to provide the tidal correction for various precision geodesy. The proposal method may also be applied to the effect of other surface loading except oceanic tides.     

KINETICS AND MECHANISM OF PHOTOINDUCED POLYMERIZATION BY α,α-DIMETHOXY-α-PHENYL ACETOPHENONE

α,α-dimethoxy-α-Phenyl acetophenone (DMPA) is an efficient and thermally stable photoinitiator. Here its spectral characteristics in the transient state were shown. The transient species were identified as a benzoyl radical and a dimethoxyi benzyl radical that played a primary initiation role in polymerization. The kinetics and mechanism of the bulk polymerization of MMA were investigated. The exponent of DMPA concentration and k_p/k_1~(1/2) value were found to be 0.5 and 0.066 mol(-1/2)l~(1/2)s~(-1/2), respectively. The existence of oxygen led to obtain the polymer with higher molecular weight, which can be attributed to the occurrence of the subsequent polymerization induced by active polymer end group. In the photocrosslinking reaction, the dependence of DMPA content on initial rate has been found. A principal reason is that the sample contained higher percentage of DMPA has higher light-absorbed efficiency. In solid film, higher concentration of DMPA is permitted to be used because there is little excited state self-quenching effect in the rigid medium.     

EFFECTS OF MONOCLONAL ANTIBODY ANTIEGF RECEPTOR ON HUMAN NASOPHARYNGEAL CARCINOMA CELL AND OTHER TUMOR CELLS

Three anti-EGF receptor MoAbs were used in these studies. Administration of MoAbs 3 and 176 inhibited tumor formation in nude mice by CNE-2, a poorly differentiated nasopharyngeal carcinoma cell line and A431, an epidermoid carcinoma cell line. When the same MoAbs were used in treatment against HeLa, a cervical carcinoma, tumor growth was not affected. The number of EGF receptors and apparent dissociation constants for ~(125)I-EGF on CNE-2 and A431 was 1.3×10~(?)/cell (Kd 7.7×10~(-8)mol/L) and 1.4×10~6/cell(Kd 2.4×10~(-9)mol/L), respectively. Both MoAbs 3 and 176, capable of competing with EGF for receptor binding, showed significant tumor growth inhibition. MoAb 101 was incapable of blocking the binding of EGF to its receptor, and not as effective as MoAbs 3 and 176 in tumor growth inhibition. Our observation is that the MoAb anti-EGF receptor is cytostatic rather than cytocidal, in vitro against CNE-2 and A431.     

OHMEFENTANYL——A NEW AGONIST FOR μ-OPIATE RECEPTOR

Ohmefentanyl (F 7302, N[1-(β-hydroxy-β-phenylethyt)-3-methyl-4-piperidyl]-N-phenylpropionamide) is a potent synthetic analgesic agent. The analgesic activity of ohmefentanyl in mice is 6300 times more potent than that of morphine. The potency of ohmefentanyl in competing with specific binding of ~3H-naloxone is reduced by Na~ (100 mM) and GTP(50μM), thus suggesting the agonist properties of this compound. Binding characteristics of ~3Hohmefentanyl with mice brain P_2 fraction are studied. An important saturable, specific and reversible binding is demonstrated. Scatchard analysis indicates the existence of two classes of binding sites (KD_1=0.32nM, KD_2=3.91nM). Various opiate drugs strongly inhibit the binding of ~3H-ohmefentanyl, but nonopiate drugs have negligible affinity. Comparison of the relative potencies of morphine, DSTLE(Tyr-D-Ser-Gly-Phe-Leu-Thr, a specific ligand for the δ-opiate receptor) and ohmefentanyl in competing with ~3H-dihydromorphine (μ) and ~3H[D-Ala~2, D-Leu~5]-enkephalin (     

Assembly-enhanced triplet-triplet annihilation upconversion in the aggregation formed by Schiff-base Pt(Ⅱ) complex grafting-permethyl-β-CD and 9,10-diphenylanthracence dimer

Water-soluble triplet sensitizer with permethyl-β-cyclodextrin(PMCD) grafting on a Schiff-base Pt(Ⅱ)complex(Pt-2),in which PMCD unit serves as a host for binding the acceptors and the Schiff-base Pt(Ⅱ)complex serves as a triplet sensitizer,was synthesized to investigate the effect of supramolecular complexation and assembly on the triplet-triplet annihilation upconversion emission in water.9,10-Diphenylanthracence(DPA) carboxylate(A-1) and its dimer(A-2) in which two DPA carboxylate were covalently linked with an alkyl chain were synthesized as triplet acceptors which also play a role of guest molecules for PMCD.A-1 and A-2 showed high affinity with PMCD,and A-2 can readily aggregate in water and form micron sized assemblies due to the hydrophobic effect and π-π stacking of anthracene core in A-2.The efficiency of TTA-UC was demonstrated to be enhanced by a synergistic effect of host-guest complexation of Pt-2 with A-2 and the self-aggregation of the acceptor A-2,which facilitated the energy transfer and energy fusion among donor and acceptor.     

THE ROUTE OF INCORPORATION OF NITROGEN ATOM INTO RIFAMYCIN DURING ITS BIOSYNTHESIS

In this paper, it was first shown that under various conditions of nitrogen supply therifamycin yield was positively correlated with the mycelial specific activity of glutaminesynthetase (GS), then the enhancing effect of glutamine, the product of GS, on rifamycin bio-synthesis was demonstrated with resting cell system. The stimulatory effect of glutaminewas more pronounced than that of glutamate, and not reduced by a GS specific inhibitor, DON.However, the increase in yield brought about by glutamate, and by asparagine was stronglyinhibited by this inhibitor. Glutamine-CO~(15)NH_2 and glutamato-α-~(15)NH_2 were synthesized andcompared for the incorporation of ~(15)N into rifamycin. It was found that the amide nitrogenwas incorporated to a much greater extent than the α-amino nitrogen, showing that glutaminewas a direct precursor of the nitrogen atom in rifamycin. In addition, synthesis of A-32(C_7N), an intermediate secreted by an inactive mutant rif 1, was also greatly stimulatedby glutamine, and the synthetic C_7N was found to be able to stimulate the biosynthesis ofrifamycin. Based upon the above results, the route of incorporation of nitrogen atom into rifamycinis summarized as follows:     

THE ELECTROCHEMICAL PREPARATION OF POLYPHENOL WITH CONDUCTIBILITY

Polyphenol film deposited on platinum foil can continuously grow with time during the electrolysis of a phenolsolution consisting of 0. 1 mol L~(-1) phenol, 3 mol L~(-1) NaOH and 0.5 mol L~(-1) Na_2SO_4, as has been proved by the methods ofsweep potential, constant potential and constant current, and visible spectra during the electrolysis of phenol. A polyphenolfilm with thickness of 0.11 mm was obtained by the electrolysis of phenol at a constant potential of 0.70 V (versus Ag/AClwith saturated KCl solution). Polyphenol film is inactive and stable in 2 mol L~(-1) H_2SO_4 solution, neutral solution and3 mol L~(-1) NaOH solution and in the potential range between -0.95 and 1.35 V. The usable potential range is dependent onthe pH value. Polyphenol has an ESR signal with a g factor of 2.0049. The conductivity of polyphenol is 1.2×10~(-4) S cm~(-1). Inthe solution of polyphenol dissolved in DMSO, the mobility of polyphenol anions is 8×10~(-9) m~2 s~(-1) V~(-1) at 20℃.     

Endonuclease-based Method for Detecting the Sequence Specific DNA Binding Protein on Double-stranded DNA Microarray

The double-stranded DNA (dsDNA) probe contains two different protein binding sites. One is for DNA- binding proteins to be detected and the other is for a DNA restriction enzyme. The two sites were arranged together with no base interval. The working principle of the capturing dsDNA probe is described as follows: the capturing probe can be cut with the DNA restriction enzyme (such as EcoR I) to cause a sticky terminal, if the probe is not bound with a target protein, and the sticky terminal can be extended and labeled with Cy3-dUTP by DNA polymerase. When the probe is bound with a target protein, the probe is not capable to be cut by the restriction enzyme because of space obstruction. The amount of the target DNA binding proteins can be measured according to the variations of fluorescent signals of the corresponding probes.     

STUDIES ON THE MECHANISM OF INDIRUBIN ACTION IN THE TREATMENT OF CHRONIC GRANULOCYTIC LEUKEMIA——V.BINDING BETWEEN INDIRUBIN AND DNA AND IDENTIFICATION OF THE TYPE OF BINDING

The binding between indirubin and calf thymus DNA in vitro has been verified by meansof the isotope labelling method, spectrophotometric method and thermal denaturation meas-urements. The λ_max 207 nm of indirubin shifted toward longer wave length with decrease ofabsorbance after the incubation of indirubin with DNA. The escalation of Tm value of DNAinduced by indirubin was about 2.4°C and it was reproducible. The binding force between themwas rather weak, as indirubin molecules were easily released during the precipitation withalcohol or the gel filtration. The binding was not affected by sodium chloride even at high con-centration but greatly decreased (to 20-30% of the control) in the presence of 8 M urea.These results showed that the binding between indirubin and DNA might be of hydrogen bondrather than ionic. The amount of bound ~3H-indirubin was directly proportional to the con-centration of indirubin. However, it increased abruptly when the concentration of indirubinreached 1.5×10~(-4) M. This     

STUDIES ON THE POLAROGRAPHIC ADSORP-TIVE COMPLEX WAVE OF RARE EARTH-ERIOCHROME AZUROL B (Ⅱ)

The rare earth ions form complexes with ECAB in 0.1 mol/L NaAc-HAc supporting electrolyte at pH 6. The composition of the complex was determined by spectrophotometric method to be 1: 2. The decrease of SAC peak height of ECAB is proportional to the concentration of rare earth ions in the range of 1×10~(-6)-2×10~(-5) mol/L. The reduction mechanism of ECAB and RE-ECAB is proposed based on the experimental evidence. The complexing group of ECAB with RE ions iust is the redox group, so when RE ions are added, there is no new peak appearing in the polarograms:, the only phenomenon observed is that the peak current of ECAB decreases. The fast protonation of EGAB carbanion formed after the second electron transfer results in the formation of colourless tetrahedral molecules.