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1.
Membranes from house fly heads were tested for the presence of mucarinic acetylcholine receptors using as a probe [3H]quinuclidinyl benzilate ([3H]QNB). Based on the presence of saturable and reversible high-affinity binding of [3H]QNB, which is inhibited by muscarinic drugs, it is suggested that these sites may be muscarinic receptors. However, these putative muscarinic receptors differ in several characteristics from the ones in mammalian brain. They have lower affinities for muscarinic drugs and lower stereoselectivity, a relatively higher affinity for the nicotinic antagonist d-tubocurarine, a lower Hill coefficient for binding of muscarinic antagonists, and a lower concentration relative to α-bungarotoxin binding sites in the same membranes. Also, unlike mammalian muscarinic receptors, they are sensitive to treatments with N-ethylmaleimide and 5,5′-dithiobis(2-nitrobenzoic acid). The effect of reduction of disulfide bonds by dithiothreitol or mercaptoethanol suggests that only the insect receptor has one or more disulfide bonds which are important to binding. On the other hand, the putative muscarinic receptors of both insect and mammalian brains have important SH group(s), whose alkylation by p-chloromercuribenzoate inhibits binding. Also, chlorobenzilate is equally effective in inhibiting [3H]QNB binding to muscarinic putative receptors of house fly and bovine brains.  相似文献   

2.
A muscarinic acetylcholine receptor (mAChR) has been demonstrated and partially characterized in larvae of the cattle tick Boophilus microplus. Its properties are compared with mAChR from an epithelial cell line from the dipteran insect Chironomus tentans. Competition studies with cholinergic ligands of different specificity revealed the muscarinic nature of the cholinergic receptors investigated in both species. In homogenates from tick larvae, specific binding sites for [3H]quinuclidinyl benzilate (QNB) with high affinity (1·2±(0·13) nM ; Bmax 22·5 pmol mg protein−1) were detected that do not bind nicotinic compounds specifically. The estimated IC50 values for nicotine, imidacloprid and α-bungarotoxin were all in the mM range. Additionally, with tick larvae, high-affinity nicotinic binding sites were detected with [3H]nicotine which could be displaced by high concentrations of imidacloprid or QNB. The estimated IC50 values for nicotine, α-bungarotoxin, imidacloprid and QNB were 43(±8) nM , 0·8(±0·2) μM , 2·8(±0·6) μM and 78(±1·9) μM , respectively. With homogenates of the non-neuronal insect cell line from C. tentans, only high-affinity binding sites for [3H]QNB were found. Muscarinic antagonists selectively displaced [3H]quinuclidinyl benzilate (QNB) binding to tick larvae homogenates. The mAChR of B. microplus preferred pirenzepine (IC50 2·13(±1·02) μM ) among different subtype-specific mAChR antagonists (4-DAMP had IC50 49·9(±9·13) μM and methoctramine had IC50 121(±14·2) μM ) indicating a type of binding site similar to the vertebrate M1 mAChR subtype. The tick muscarinic receptor seems to be a G-protein-coupled receptor, as concluded from the 4·8-fold reduction in receptor affinity for binding of the muscarinic agonist oxotremorine M upon treatment with the non-hydrolysable GTP-analogue γ-S-GTP. Binding data for the agonists oxotremorine M (IC50 71·3(±19·6) μM ) and carbachol (IC50 253(±87·1) μM ) parallel the biological efficacy of these compounds, in that, while oxotremorine M showed some activity against ticks, carbachol was ineffective.  相似文献   

3.
The interactions of natural pyrethrins and nine pyrethroids with the nicotinic acetylcholine (ACh) receptor/channel complex of Torpedo electric organ membranes were studied. None caused significant reduction in [3H]ACh binding to the receptor sites, but all inhibited [3H]perhydrohistrionicotoxin ([3H]H12-HTX) binding to the channel sites in presence of carbamylcholine. Allethrin inhibited [3H]H12-HTX binding noncompetitively, but [3H]imipramine binding competitively, suggesting that allethrin binds to the receptor's channel sites that bind imipramine. The pyrethroids were divided into two types according to their actions: type I, which included pyrethrins, allethrin, bioallethrin, resmethrin, and tetramethrin, was more potent in inhibiting [3H]H12-HTX binding and acted more rapidly (i.e., in <30 sec). Type II, which included permethrin, fluvalinate, cypermethrin and fenvalerate, was less potent and their potency increased slowly with time. Also, inhibition of the initial rate of [3H]H12-HTX binding by type I compounds increased greatly by the presence of the agonist carbamylcholine, but this was not so with type II compounds. The receptor-regulated 45Ca2+ flux into Torpedo microsacs was inhibited by pyrethrins and pyrethroids, suggesting that their action on this receptor function is inhibitory. There was very poor correlation between the potencies of pyrethrins and pyrethroids in inhibiting [3H]H12-HTX binding and their toxicities to house flies, mosquitoes, and the American cockroach. However, the high affinities that several pyrethroids have for this nicotinic ACh receptor suggest that pyrethroids may have a synaptic site of action in addition to their well known effects on the axonal channels.  相似文献   

4.
Repeated exposures to anti-cholinesterase compounds induce profound enzyme inhibition and consequent neurotransmitter perturbations. When the result of exposure is an accumulation of neurotransmitter, as it is in the case of exposure to soman, target receptors may respond by compensating for the imbalance by regulating either their number or binding affinity. Recovery of function may further include alterations in receptor systems not themselves a direct target of the toxic compound. Rats were injected with soman (50 μg/kg, sc) three times weekly for 4 weeks and decapitated at intervals ranging from 1 hr to 6 days after the final injection. Synaptic membranes were prepared from hippocampus (HIP), striatum (STR), and cortex (COR) and kinetics of muscarinic cholinergic and GABAergic binding were assessed using [3H]QNB and [3H]muscimol, respectively, as ligands. Soman induced large and persistent decreases in the number of muscarinic receptors in HIP and COR with the surviving receptors being of higher affinity. The number of high affinity GABA receptors decreased in all three regions but returned to near baseline within 3 days after the final soman exposure. These effects are due either to a direct action of soman on the receptors, or a diaschitic response of the receptors to cholinergic excess. Muscarinic cholinergic receptors exhibit a persistent down regulation, and GABA receptors a transient response, to soman administration.  相似文献   

5.
Desnitroimidacloprid (desnitro-IMI) is proposed to be a bioactivation product of imidacloprid and to bind at the same site as [3H]nicotine in the nicotinic acetylcholine receptor (nAChR) of mouse brain membranes. The α4β2 nAChR subtype accounts for >90% of the binding sites for nicotine in rat brain. This study further characterizes the binding site for [3]desnitro-IMI and [3H]nicotine in rat recombinant α4β2 nAChR using receptor expressed in Sf9 insect cells so that the assays involved no other receptor subtypes or interference from metabolic activation and detoxification systems. The two radioligands gave the same Bmax of 7.5 pmol/mg protein and apparent Kd values of 3.3 nM for nicotine and 8.9 nM for desnitro-IMI by Scatchard analysis at 22°C. However, at 4°C, the observed apparent association rate is slower and dissociation rate is faster for [3H]desnitro-IMI than for [3H]nicotine and due to the rapid rate of dissociation of [3H]desnitro-IMI the Kd calculated from the determined association and dissociation rates more closely approximates 1.0 for both ligands. Eight cholinergic agents and nine nicotinoids are equipotent in displacing [3H]desnitro-IMI and [3H]nicotine, with IC50 values (nM) of 0.5 for epibatidine, 1 for cytisine, 4–6 for nicotine and desnitro-IMI, 15 for acetylcholine, and 155 for imidacloprid, with an overall correlation for inhibitor potencies of r2 = 0.99 (n = 17). This correlation of binding site properties extends to [3H]nicotine in the recombinant α4β2 receptor and rat brain membranes (r2 = 0.99, n = 12). Thus, desnitro-IMI and nicotine bind with high affinity to the same site in rat recombinant α4β2 neuronal nAChR. This recombinant receptor can be generated in sufficient quantities for high-throughput target site screening and structural analysis of the binding site.  相似文献   

6.
[3H]Flunitrazepam ([3H]Flu) was used to identify benzodiazepine binding sites in house fly thorax muscle membranes using a filter assay. [3H]Flu bound to a finite number of sites in a concentration- and time-dependent manner, reaching equilibrium in 10 min. Scatchard plots of the binding indicated a high-affinity site at 0.2 pmol/mg protein (Kd 24.3 nM) and a low-affinity site at 8.2 pmol/mg protein (Kd994nM). Binding of [3H]Flu to the high-affinity binding site was inhibited by several benzodiazepine analogs, with Flu, diazepam, and Ro 5-4864 being more potent than β-CCE, Ro 5-3027, and Ro 5-2180. Clonazepam was least potent in inhibiting [3H]Flu binding. Thus, the drug specificity of these insect muscle benzodiazepine binding sites was quite different from both the mammalian central and peripheral benzodiazepine receptor sites, though closer to the peripheral ones. GABA (γ-aminobutyric acid) and its agonists enhanced the specific binding of [3H]Flu in a dose-dependent manner, and this effect was inhibited with the GABA antagonist bicuculline. The effect was biphasic since at high GABA concentrations this stimulation was reduced. The data suggest that house fly muscles have benzodiazepine receptors, which are coupled allosterically to GABA receptors, analogous to the GABA/benzodiazepine receptors of vertebrates, but with some differences in their drug specificities.  相似文献   

7.
Buprofezin (Applaud, 2-tert-butylimino-3-isopropyl-5-phenyl-3,4,5,6-tetrahydro-2H-1,3,5-thiadiazin-4-one) strongly inhibited the [3H]chitin synthesis from N-acetyl-d-[1-3H]glucosamine in the brown rice planthopper, Nilaparvata lugens Stål. No inhibition was observed for [3H]-labeled protein biosynthesis from [5-3H]glucose or l-[3,5-3H]tyrosine but [3H]-labeled nucleic acid synthesis from [5-3H]glucose was weakly reduced by buprofezin. The lethal activity of buprofezin analogs related well to their inhibitory potency against chitin biosynthesis in N. lugens nymphs.  相似文献   

8.
l-[U-14C]sucrose accumulation by phloem sieve tube members (PSTM) of wheat (Triticum aestivum L. ‘Holley’) and sorghum (Sorghum bicolor L. ‘G522 DR’) was inhibited by the nonpermeant sulfhydryl inhibitor p-chloromercuribenzenesulfonic acid (PCMBS), and this inhibition was reversed by the permeant sulfhydryl protectants dithiothreitol (DTT) and dithioerythritol (DTE). S-Ethyl dipropylthiocarbamate (EPTC) (≤0.1 mM) did not inhibit [14C]sucrose accumulation by wheat or sorghum PSTM. N-N-Diallyl-2-chloroacetamide (CDAA) (1 mM) inhibited [14C]sucrose accumulation by sorghum but not by wheat PSTM. The inhibition of [14C]sucrose accumulation in sorghum PSTM by the membrane permeant CDAA was reversed by DTT. Sorghum growth was inhibited by <1 μM CDAA. Membrane permeant 2-chloroallyl diethyldithiocarbamate (CDEC) (0.1 mM) inhibited [14C]sucrose accumulation by PSTM of sorghum but not wheat. The inhibition of sucrose accumulation in sorghum PSTM by 0.1 mM CDEC was reversed by DDT.  相似文献   

9.
Anthranilic and phthalic diamides exemplified by chlorantraniliprole (Chlo) or cyantraniliprole (Cyan) and flubendiamide (Flu), respectively, are the newest major chemotype of insecticides with outstanding potency, little or no cross resistance with other classes and low mammalian toxicity. They are activators of the ryanodine (Ry) receptor (RyR)-Ca2+ channel, based on Ca2+ flux and electrophysiology investigations. The goal of this study is to define species differences in the degree and mechanisms of diamide selective action by radioligand specific binding studies at the [3H]Ry, [3H]Chlo and [3H]Flu sites. The [3H]Ry site is observed in muscle of lobster, rabbit and four insect species (Musca domestica, Apis mellifera, Heliothis virescens and Agrotis ipsilon) whereas the [3H]Chlo site is evident in the four insects and the [3H]Flu site in only the two lepidoptera (Agrotis and Heliothis). [3H]Ry binding is significantly stimulated by Chlo, Cyan and Flu with the insects (except Flu with Musca) but not the lobster and rabbit. [3H]Chlo binding is stimulated by Ry and Flu in Musca and Apis but not in the lepidoptera, while Flu and Cyan are inhibitory. [3H]Flu binding is strongly inhibited by Chlo and Cyan in Agrotis and Heliothis. [3H]Chlo and [3H]Flu binding are not dependent on added Ca2+ or ATP in Heliothis and Agrotis whereas the other radioligand-receptor combinations are usually enhanced by Ca2+ and ATP. More generally, there are species differences in the Ry, Chlo and Flu binding sites of the RyR that may confer selective toxicity and determine target site cross resistance mechanisms.  相似文献   

10.
γ-Aminobutyric acid (GABA) receptors (GABARs) are an important target for existing insecticides such as fiproles. These insecticides act as noncompetitive antagonists (channel blockers) for insect GABARs by binding to a site within the intrinsic channel of the GABAR. Recently, a novel class of insecticides, 3-benzamido-N-phenylbenzamides (BPBs), was shown to inhibit GABARs by binding to a site distinct from the site for fiproles. We examined the binding site of BPBs in the adult housefly by means of radioligand-binding and electrophysiological experiments. 3-Benzamido-N-(2,6-dimethyl-4-perfluoroisopropylphenyl)-2-fluorobenzamide (BPB 1) (the N-demethyl BPB) was a partial, but potent, inhibitor of [3H]4′-ethynyl-4-n-propylbicycloorthobenzoate (GABA channel blocker) binding to housefly head membranes, whereas the 3-(N-methyl)benzamido congener (the N-methyl BPB) had low or little activity. A total of 15 BPB analogs were tested for their abilities to inhibit [3H]BPB 1 binding to the head membranes. The N-demethyl analogs, known to be highly effective insecticides, potently inhibited the [3H]BPB 1 binding, but the N-methyl analogs did not even though they, too, are considered highly effective. [3H]BPB 1 equally bound to the head membranes from wild-type and dieldrin-resistant (rdl mutant) houseflies. GABA allosterically inhibited [3H]BPB 1 binding. By contrast, channel blocker-type antagonists enhanced [3H]BPB 1 binding to housefly head membranes by increasing the affinity of BPB 1. Antiparasitic macrolides, such as ivermectin B1a, were potent inhibitors of [3H]BPB 1 binding. BPB 1 inhibited GABA-induced currents in housefly GABARs expressed in Xenopus oocytes, whereas it failed to inhibit l-glutamate-induced currents in inhibitory l-glutamate receptors. Overall, these findings indicate that BPBs act at a novel allosteric site that is different from the site for channel blocker-type antagonists and that is probably overlapped with the site for macrolides in insect GABARs.  相似文献   

11.
The calcium channel and the ‘calcium release channel’ of muscle membrane of the cockroach Periplaneta americana have been characterized. Biological assays with calcium channel blockers and ryanodine on different insects and acari revealed pronounced insecticidal effects with ryanodine, but not with calcium channel blockers, at concentrations between 0·1 and 300 μg ml−1. Skeletal muscle membranes derived either from the tubular network or from the sarcoplasmatic reticulum of P. americana were characterized with respect to the binding of the dihydropyridine (DHP) [3H]isradipine (PN 200-110), the phenyl-alkylamine [3H]verapamil and the alkaloid [3H]ryanodine. Preliminary binding studies with the benzothiazepine [3H]diltiazem suggest a low-affinity binding site with a IC50 value of 3·3 μM . All binding sites tested were sensitive to treatment with proteinase K. Optimal conditions for binding of the radioligand ryanodine revealed the highest specific binding at pH 8 and at calcium chloride concentrations between 100 and 500 μM . EGTA at 10 μM abolished 95% of the ryanodine binding. Binding studies with calcium channel binding sites revealed a pronounced effect of low Ca2+ concentrations on specific isradipine binding, whereas verapamil and diltiazem binding were only reduced by the presence of 200 μM EGTA. With respect to high Ca2+ concentrations, specific binding of diltiazem, isradipine and verapamil was reduced by 73, 40 and 20%, respectively, at 5 mM Ca2+. Radioligand binding experiments showed high-affinity binding sites for ryanodine and isradipine. KD values of 0·95 nM (Bmax=550 fmol mg−1 protein) and 0·75 nM (Bmax=213 fmol mg−1 protein) were determined respectively. A lower-affinity binding site was identified in binding studies with verapamil (KD=7·4 nM and Bmax=27 fmol mg−1 protein). [3H]isradipine displacement studies with several dihydropyridines revealed the following ranking of affinity: nitrendipine>isradipine>Bay K8664≪nicardipine. Displacement of [3H]verapamil binding by effectors of the phenylalkylamine binding site showed that bepridil and S(-)verapamil had the highest affinities of the compounds tested followed by (±)verapamil, nor-methylverapamil and R(+)verapamil.  相似文献   

12.
A series of known agonists of the mammalian muscarinic receptor were prepared and evaluated for their insecticidal potential. It was discovered that pests such as Nilaparvata lugens (brown planthopper), Nephotettix cincticeps (green leafhopper), Tetranychus urticae (two-spotted spider mite) and Aphis gossypii (cotton aphid) were particularly sensitive to most of these compounds. Several analogs proved to be extremely active, surpassing commercial standards in some of the laboratory bioassays. These compounds exhibited a range of potencies for the insect (Musca) muscarinic receptor. Addition of GTP significantly reduced the affinity of the most potent analog for the Musca mAChR, indicating the compound functions as an agonist in insect tissue. Regression analysis indicated that significant relationships exist between displacement of [3H]QNB at the Musca muscarinic receptor and whole organism toxicity to three insect and one mite species. The results suggested that the insect muscarinic receptor represents a viable target site for insecticidal action. © 1997 SCI.  相似文献   

13.
The binding behavior of mercuric chloride (HgCl2), phenylmercuric acetate (PMA), and ethylmercuric chloride (EMC) to the spinach chloroplasts in relation to the inhibition of the Hill reaction was studied at pH 6.8 and 7.8 using 203Hg labeled compounds. The pH of the reaction medium did not influence the amount of mercury binding of the chloroplast at various mercurial concentrations, but it altered the inhibition curve of the Hill reaction. Between 0–1 × 10?5M the binding of Hg2+ and EMC were similar and increased linearly with the concentration, while the binding of PMA was similar to the binding of Hg2+ only at a concentration below 4 × 10?6M and was less when the concentration was above 4 × 10?6M. However, the inhibition of the Hill reaction by these mercury compounds was quite different; at pH 7.8, the I50 values for Hg2+, PMA, and EMC were 5 × 10?6, 2.5 × 10?6, and 2.5 × 10?6M, respectively, while at pH 6.8, these values were 4 × 10?6, 4 × 10?5, and 2 × 10?4M, respectively. The differential block of electron flow by the mercury compounds at pH 6.8 and 7.8 was further confirmed by electron spin resonance study.  相似文献   

14.
A study was conducted concerning the inhibition of calf thymus nuclear DNA synthesis by captan. Captan was shown to be toxic to the in vitro incorporation of [3H]dTTP into calf thymus DNA, with an ID50 value of 0.16 mM being measured. This inhibition was determined to be independent of Mg2+ concentration. Although intact nuclear activities were affected, the soluble DNA polymerizing activity isolated from calf thymus nuclei exhibited no inhibition when exposed to captan. Treatment of purified calf thymus DNA with 10?5 and 10?4M captan caused an elevation of the Tm by 2 and 6°C, respectively. The inhibitory characteristic of captan on DNA polymerizing activities and the influence of this compound on the thermostability of DNA indicate a mechanism of inhibition which is located in the nucleus and is possibly related to the template function of DNA and/or with the nuclear DNA polymerizing enzymes.  相似文献   

15.
This study attempts to use [3H] α-endosulfan to examine directly the binding site(s) for cyclodienes, lindane and toxaphene (collectively referred to as the polychlorocycloalkane or PCCA insecticides) in the 4-aminobutyric acid (GABA)-gated chloride channel. [3H] α-Endosulfan was prepared by reduction of hexachloronorbornenedicarboxylic anhydride with sodium borotritide, then coupling the labelled alcohol with thionyl chloride followed by HPLC purification (35 Ci mmol?1, > 99% radiochemical purity). This new candidate radioligand readily partitions into lipid membranes and undergoes indiscriminate adsorption to surfaces resulting in high levels of non-specific binding. This makes it very difficult to differentiate the small portion of specific binding at the site relevant to toxic action. This problem was partially circumvented by incubating [3H] α-endosulfan (0.1 nM) with house-fly head membranes (0.2 mg protein) for 70 min at 22°C giving 23 (±4)% specific binding (40 fmol mg?1 protein) determined as the difference between the radioligand alone and on preincubation for 15 min with unlabelled α-endosulfan (final concentration 100 nM). This procedure is not appropriate for determination of saturation isotherms and standard binding kinetics. However, the effectiveness of 16 PCCAs (also at 100 nM final concentration) in blocking the specific binding of [3H] α-endosulfan is generally consistent with their relative potencies as inhibitors of 4-[3H] propyl-1-(4-ethynylphenyl)-2,6,7-trioxabicyclo[2.2.2] octane ([3H]EBOB) binding suggesting that the binding site for both [3H]α-endosulfan and the PCCAs is part of the GABA-gated chloride channel. Insecticidal channel blockers of other types (e.g. picrotoxinin, trioxabicyclooctanes, a dithiane, and phenylpyrazoles) and GABA are poor inhibitors of [3H] α-endosulfan binding relative to their potencies as inhibitors of [3H] EBOB binding. It therefore appears that the PCCAs compete directly for the [3H] α-endosulfan site, whereas the other channel blockers bind with different inhibition kinetics or at a site more closely coupled to the EBOB than the α-endosulfan binding domain.  相似文献   

16.
The electron transport inhibition, uncoupling, and binding of ioxynil and bromoxynil salts is compared in chloroplast fragments isolated from two weed species with contrasting responses to the hydroxybenzonitriles. Ioxynil Na was three to four times more inhibitory than bromoxynil K towards DCPIP and SiMo reduction in both Matricaria inodora and Viola arvensis. Ioxynil Na was also a more potent uncoupler of PSI-dependent electron transport from ascorbate/DCPIP to methyl viologen. Uncoupling occurred at concentrations higher than those that inhibited electron transport. Binding studies with [14C]bromoxynil K and [14C]ioxynil Na salts revealed slightly biphasic curves with no significant difference in the amounts of the two herbicides bound at a given concentration. The ratios of inhibition constant (Ki) and binding constant (Kb) were approximately one for ioxynil Na and three for bromoxynil K. Radiolabelled herbicide displacement studies revealed that ioxynil Na could partially displace bound [14C]bromoxynil K, but bromoxynil K could not displace bound ioxynil Na at biochemically active concentrations. Ioxynil Na may be a more effective inhibitor than bromoxynil K because it binds more strongly to the thylakoid membrane.  相似文献   

17.
The mode of action of DDT and pyrethroids was investigated in the house fly, Musca domestica L, using drug:receptor binding techniques. Both in vivo and in vitro binding studies demonstrated the existence of membrane receptors which bind specifically to [14C]DDT and [14C]cis-permethrin. The receptors show properties to be expected of a critical target site of these insecticides. These include negative temperature correlation with binding, relatively nonsensitivity to DDE, and sensitivity to Ca2+. The receptor sites are readily saturated at 45–90 nM [14C]DDT and have an apparent disassociation constant (Kd) of 12.2 nM. The maximum number of binding sites was estimated to be 17 pmol DDT/mg membrane protein (0.34 pmol/house fly head). Competition studies showed DDT, cis-permethrin, and cypermethrin bind to the same receptor but not at precisely the same site. The addition of Ca2+ to the incubation buffer significantly inhibited the binding of both [14C]DDT and [14C]cis-permethrin, suggesting the receptor binding is Ca2+ sensitive and may have a role in ion conductance.  相似文献   

18.
The formamidines chlordimeform, demethylchlordimeform (DCDM), amitraz and BTS-2727l were tested for their respective abilities to inhibit [3H]mianserin binding in membrane preparations of cockroach brain and, in the same tissue, to stimulate octopamine-sensitive receptors coupled to adenylate cyclase. Analysis of [3H]mianserin binding indicated negative cooperativity between two binding sites with respective Kd and Bmax values of 3.82 mM and 0.886 pmol (mg protein)?1 for a high-affinity site and 218 nM and 13.56pmol (mg protein)?1 for a low-affinity site. DCDM, BTS-27271 and amitraz inhibit [3H]mianserin binding with IC50 values similar to those obtained with octopamine and the μ-adrenergic antagonist, phentolamine, whereas chlordimeform is a poor competitor for the binding sites. Similarly DCDM, BTS-27271 and amitraz elevate cyclic AMP production in brain membrane preparations in a dose-dependent manner with Ka values of 0.32 uM, 1.5 uM and 3.4 uM respectively, whereas chlordimeform was again without effect. The formamidine-mediated responses were fully additive with the evaluation of cyclic AMP obtained using the maximal concentration of dopamine but not with octopamine-mediated increases; thus the formamidine effects appear to be expressed through partial agonism of octopamine receptors that are coupled to adenylate cyclase.  相似文献   

19.
刘长春 《农药学学报》2015,17(1):97-100
以芳香硝基化合物、2-氯-5-吡啶甲醇和一氧化碳为原料,在Pd-Fe/Ti O2催化下进行羰基化反应,合成了11个新型氨基甲酸-2-氯吡啶-5-甲酯化合物,其结构经1H NM R和M S表征。初步抑菌活性测定结果表明:在50 mg/L下,大多数目标化合物对4种供试病原菌具有一定的抑制活性,其中化合物3f(4-甲氧基苯基氨基甲酸-2-氯吡啶-5-甲酯、3h(2,4-二氯苯基氨基甲酸-2-氯吡啶-5-甲酯)和3j(3,4-二氯苯基氨基甲酸-2-氯吡啶-5-甲酯)对小麦赤霉病菌Gibberella zeae的抑制率达77.3%以上,3f对苹果轮纹病菌Physalospora piricola的抑制率达82.5%,与对照药多菌灵接近;所有化合物在50 mg/L下对番茄灰霉病菌Botrytis cinerea的抑制活性均优于对照药多菌灵。  相似文献   

20.
5-tert-Butyl-2-(4-ethynylphenyl)pyrimidine and the corresponding 2,5-disubstituted-4H-1,3-thiazine block the GABA-gated chloride channel at c.20and c.200 nm , respectively, measured as 50% inhibition of the binding of 1-(4-ethynylphenyl)-4-[3H]propyl-2,6,7-trioxabicyclo[2.2.2]octane (4′-ethynyl-4-n-[3H]propylbicycloorthobenzoate; [3H]EBOB) in house fly and mouse brain membranes, and they are also toxic to topically-treated flies with LD50 values of 6–27 μg g−1 alone and 2–6 μg g−1 with piperonyl butoxide (PB) as synergist. In the pyrimidine series, the general pattern of effectiveness of substituents in the 5-position is tert-butyl>isopropyl≈cyclohexyl≈cyclopropyl>methyl, phenyl and 3- and 4-fluorophenyl, and in the 2-position is 4-ethynylphenyl≪4-bromophenyl. These planar pyrimidines and nearly-planar 4H-1,3-thiazines with 2-ethynylphenyl or 2-bromophenyl and 5-tert-butyl or 5-isopropyl substituents are more effective than the corresponding 6H-1,3-thiazine, 6-oxo-1,3-thiazines and 4,6-dioxo-1,3-thiazine examined, but they are less active than the analogous conformationally flexible trans-1,3-dioxanes and -1,3-dithianes. The heterocyclic moiety confers a region of high electron density and positions the 2- and 5-substituents in a linear or parallel relationship for optimal affinity at the receptor. Two observations indicate that the new pyrimidines and thiazines probably act as chloride channel blockers. First, the poisoning signs are identical to those of EBOB in both mice and house flies. Second, each of the pyrimidines, thiazines and dioxanes falls on the same correlation line for inhibition of [3H]EBOB binding and toxicity to house flies (with PB) as that obtained earlier for EBOB analogs, dithianes and polychlorocycloalkanes, suggesting that they all act at the same or closely coupled binding sites in the GABA-gated chloride channel.  相似文献   

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