Biomedical subjects

A Hirashima

Publications and source records attributed to A Hirashima.

At least 19 recordsLinked to original sources

PubMed2004

Comparative receptor surface analysis of agonists for tyramine receptor which inhibit sex-pheromone production in Plodia interpunctella.

The quantitative structure-activity relationship (QSAR) of a set of 29 agonists for tyramine (TA) receptor responsible for the inhibition of sex-pheromone production in Plodia interpunctella, was analyzed using comparative receptor surface analysis (CoRSA). Using the common steric and electrostatic features of the most active members of a series of compounds, CoRSA generated a virtual receptor model, represented as points on a surface complementary to the van der Waals or Wyvill steric surface of the aligned compounds. Three-dimensional energetics descriptors were calculated from receptor surface model (RSM)/ligand interaction and these three-dimensional descriptors were used in genetic partial least squares data analysis to generate a QSAR model, giving a 3D QSAR with r(2)=0.969 for calibration and CV- r(2)=0.635 for the leave-one-out cross validation.

Animals↗

PubMed2001

Identification of novel inhibitors of calling and in vitro [14C]acetate incorporation by pheromone glands of Plodia interpunctella.

Some octopamine agonists were found to suppress in vitro biosynthesis of the calling pheromone of the Indian meal moth, Plodia interpunctella. Isolated pheromone-gland preparations incorporated sodium [14C]acetate at a linear rate for 3 h when incubated with the pheromone biosynthesis activating neuropeptide (PBAN). This incorporation was dependent on the dose of PBAN (up to 0.5 microM). Thin-layer chromatography of a pheromone-gland extract revealed quantitative incorporation of radioactivity into a product exhibiting the same mobility as (Z,E)-9,12-tetradecadienyl acetate, the main component of the calling pheromone of P interpunctella. Twenty-seven octopamine agonists were initially screened using a calling behaviour bioassay of female P interpunctella. Four derivatives with activity in the nanomolar range were identified which were, in order of decreasing pheromonostatic activity: 2-(2,6-diethylphenylimino)thiazolidine > 2-(2,6-diethylphenylimino)oxazolidine > 2-(2,6-dimethylphenylimino)thiazolidine > 2-(2-ethylphenylimino)oxazolidine. These compounds also showed in vitro inhibitory activity in intracellular de novo pheromone biosynthesis. The results of the present study indicate that these derivatives could provide useful information in the characterization and differentiation of octopaminergic receptor types and subtypes.

Adenylyl Cyclases↗

PubMed2001

[Interaction of hormones in controlling reproductive function of Drosophila females under stressful conditions is genetically determined].

The effect of heat stress (38 degrees C) on the content of octopamine (OA) and 20-hydroxyecdysone (20HE) was studied under normal and stressful conditions in adult flies of Drosophila virilis lines contrasting in the level of the juvenile hormone (JH). The wild-type flies (line 101) exhibited a pronounced sex dimorphism for the content of both OA and 20HE, which was substantially lower in this line than in flies of the mutant line 147. The level of both hormones increased in flies of line 101 exposed to heat stress, whereas it remained unchanged in flies of line 147 under the same conditions. The effect of heat stress on the level of JH metabolism and fertility was also studied in D. melanogaster wild-type lines and lines carrying mutations in genes responsible for OA and DA syntheses. In octopamineless females of the T beta hnM18 line and in females of the Ste line characterized by a doubled content of DA, JH degradation differed from normal: it was increased in both young and mature T beta hnM18 females, while decreased in young and increased in mature Ste flies. Fertility was substantially lower in the Ste than in the wild-type line. Flies of all of the D. melanogaster lines produced a stress response; however, in mutant lines, both fertility and stress reactivity of the systems controlling JH metabolism differed significantly from that of the wild-type lines. The role of JH, 20HE, OA, and DA interaction in regulation of Drosophila reproduction under stressful conditions is discussed.

Animals↗

PubMed2000

Role of ribosome recycling factor (RRF) in translational coupling.

RNA phage GA coat and lysis protein expression are translationally coupled through an overlapping termination and initiation codon UAAUG. Essential for this coupling are the proximity of the termination codon of the upstream coat gene to the initiation codon of the lysis gene (either a <3 nucleotide separation or physical closeness through a possible hairpin structure) but not the Shine-Dalgarno sequence. This suggests that the ribosomes completing the coat gene translation are exclusively responsible for translation of the lysis gene. Inactivation of ribosome recycling factor (RRF), which normally releases ribosomes at the termination codon, did not influence the expression of the reporter gene fused to the lysis gene. This suggests the possibility that RRF may not release ribosomes from the junction UAAUG. However, RRF is essential for correct ribosomal recognition of the AUG codon as the initiation site for the lysis gene.

Amino Acid Sequence↗

PubMed2000

Docking study of enantiomeric fonofos oxon bound to the active site of Torpedo californica acetylcholinesterase.

Molecular interaction between enantiomeric fonofos oxon (O-ethyl S-phenyl ethylphosphonothiolate) and acetylcholinesterase (AChE) of Torpedo californica was evaluated by using the Cerius2 program. It was suggested that the difference in the inhibitory activity of the two enantiomers of fonofos oxon on AChE is due to the steric hindrance in binding to the AChE active site.

Acetylcholinesterase↗

PubMed2000

Quantitative structure-activity studies of octopaminergic agonists and antagonists against Locusta migratoria using similarity indexes.

The quantitative structure-activity relationship of 39 octopamine (OA) agonists and 12 antagonists against the thoracic nerve cord of the migratory locust, Locusta migratoria L. was analyzed using atom based rigid fit method or flexible fitting offered by PowerFit 1.0 from MicroSimulation. For OA agonists, the more similar to reference compound NC (24) the structure of test compound, the higher the activity, whereas for OA antagonists it was not the case. Antagonists may not interact with the same part of the membrane with which the agonists interact. Taken the part of the membrane with which the agonist interacts as the true receptor, the antagonist may well interact with an area surrounding the receptor including the ionophore.

Animals↗

PubMed2000

Biogenic amines in Drosophila virilis under stress conditions.

The effect of heat stress (38 degrees C) on the content of DL-beta-(3,4-dihydroxyphenyl)alanine (DOPA), dopamine, tyramine, octopamine, and their precursor Tyr was studied in adults of two lines of Drosophila virilis contrasting in their stress response. In individuals of line 101 responding to stress by a hormonal stress reaction, the contents of DOPA, dopamine, octopamine, and Tyr were lower than those of line 147 that did not respond to the stress. However, heat stress caused an increase in the contents of DOPA, dopamine, octopamine, and Tyr in line 101, whereas the equivalent titers in line 147 remain unchanged.

Adaptation, Physiological↗

PubMed2000

Ecdysteroids in stress responsive and nonresponsive Drosophila virilis lines under stress conditions.

After exposure to thermal stress or a control temperature, the relative abundance of ecdysone (E) and 20-hydroxyecdysone (20E) was measured in a wild-type line of Drosophila virilis (101) that is stress responsive and in a mutant line (147) that is not stress responsive. In line 101, the 20E content was higher and E content lower in females than in males. The abundance of E and 20E in females of line 147 was significantly higher than that in females of line 101. Females of line 101 were found to respond to 60 min of heat stress (38 degrees C) by an increase in the abundance of both E and 20E, while in males of this line the amount of 20E increased and that of E declined. A role of the ecdysteroids in the control of reproduction of D. virilis under stress is discussed.

Adaptation, Physiological↗

PubMed2000

Genetic control of biogenic-amine systems in Drosophila under normal and stress conditions.

The contents of octopamine and its precursors (tyrosine and tyramine) were studied in adults of two lines of Drosophila virilis with contrasting stress responses. It was demonstrated that in individuals responding to stress by a hormonal stress reaction (line 101), the contents of octopamine and tyrosine are lower than in nonresponding flies (line 147). It was found that there is no difference between the lines in the level of tyramine under normal conditions. The dopamine response to stressor was also studied. Genetic analysis of these differences revealed that they are controlled by a single gene and that the gene is not sex-linked. The gene controlling the response was found to be linked to chromosome 6 of D. virilis.

Animals↗

PubMed1999

Effect of octopamine on the activity of juvenile-hormone esterase in the silkworm Bombyx mori and the red flour beetle Tribolium freemani.

This study focuses on the effect of octopamine (OA) on metamorphosis of the silkworm Bombyx mori and the red flour beetle Tribolium freemani Hinton. Titers of OA and juvenile-hormone esterase (JHE) were measured at various larval and pupal stadia of both insects. Effects of OA, OA agonists, and antagonists on metamorphosis and JHE activity were also examined. At day 2, peaks of OA and JHE activity were observed in third instars, and at day 3, a sharp peak of OA was observed, followed by a large peak of JHE activity at day 4 in last instars of B. mori. However, no peaks of OA and JHE activity were observed in fourth instars. A high titer of OA appeared at days 2-4, followed by a peak of JHE activity at day 7 and the second OA peak at day 9 after the start of assay of T. freemani. At pupation, a small peak of OA and the highest activity of JHE were observed. The effects of OA on JHE activity were examined in vitro, because the relationship could be responsible for triggering pupation in B. mori and T. freemani larvae. Exogeneous OA (0.1-10 mM) stimulated the JHE activity of final instars (day 2) of B. mori in vitro. Similarly, the presence of OA (10 mM) activated the JHE activity of newly ecdysed T. freemani pupae in vitro. OA antagonists chlorpromazine and gramine delayed the start of spinning and reduced the JHE activity of B. mori, when applied in diet at 10-100 ppm. Some OA agonists stimulated the pupation and JHE activity of T. freemani larvae reared under crowded conditions, when topically applied. Thus, OA may contribute to activation of the events preparatory to a pupal molt, i.e., the secretion of OA increases JHE activity followed by stimulation of pupation.

Animals↗

PubMed1999

Titres of biogenic amines and ecdysteroids: effect of octopamine on the production of ecdysteroids in the silkworm Bombyx mori.

At day two, a sharp peak of octopamine (OA) was observed in last instar female Bombyx mori larvae. This peak also appeared in male larvae a day later than in females at day three. An OA peak was also observed before the 3rd ecdysis. However, no OA peaks were observed in 4th instar larvae. At day eight and nine of the 5th instar, another OA peak was observed for male and female, respectively. A peak of tyramine (TA) was found at day one followed by a peak of OA at day two in 3rd instar larvae. At day two, a day before OA peak, a peak of TA was observed for male insects and before the 2nd peak of OA, TA titre was also high in 5th instar larvae. Immediately after 3rd ecdysis, a high titre of DL-beta-(3,4-dihydroxyphenyl)alanine (DOPA) was observed, followed by a peak of dopamine (DA) at day five. A peak of DOPA was found at day one followed by a peak of DA at day two in 3rd instar larvae. Similarly, a small peak of DOPA was observed at day two, followed by an increase of DA at days eight and nine after the 4th ecdysis. Ecdysteroid peaks were observed just before the 3rd and 4th ecdysis and an ecdysteroid titre increased after the start of spinning. The effects of OA and JH on production of ecdysteroids by prothoracic glands (PGs) were examined in order to identify neuromediators responsible for triggering pupation in B. mori larvae. Exogeneous OA (10-100 mM) reduced and 10 &mgr;M OA stimulated the production of ecdysteroids in the presence and absence of brain extracts by PGs in the final instar (day five) of B. mori in vitro. Meanwhile, exogeneous JHI (10 &mgr;g/ml) stimulated and at 5 &mgr;g/ml it reduced production of ecdysteroids in the presence of brain extracts. Gramine, an OA antagonist, delayed pupation when applied in the diet. Thus, OA may produce some biological effects on the programming of larval-pupal development.

Journal Article↗

PubMed1999

Three-dimensional pharmacophore hypotheses for the locust neuronal octopamine receptor (OAR3). Part 2: agonists.

Three-dimensional pharmacophore hypotheses were built from a set of 43 agonists against octopamine receptor class 3 (OAR3) in locust nervous tissue. Among the 10 chemical-featured models generated by program Catalyst/Hypo, a hypothesis including hydrogen-bond acceptor (HBA), hydrophobic (Hp), and hydrophobic aliphatic (HpA1) features was considered to be important and predictive in evaluating OAR3 agonists. While the ideal and null hypotheses had a cost of 156.40 and 239.20, respectively, the 10 resulting hypotheses possessed costs from 169.89 to 175.81. The best hypothesis that was confirmed to have a 95% chance of true correlation yielded a low RMS of 0.757 and high regression r of 0.933. Active agonists mapped well onto all the features of the hypothesis such as HBA, Hp, and HpA1. On the other hand, inactive compounds were shown to be difficult to achieve the energetically favorable conformation which is found in the active molecules in order to fit the 3-D chemical feature pharmacophore models.

Animals↗

PubMed1999

Three-dimensional quantitative structure-activity studies of octopaminergic agonists responsible for the inhibition of sex-pheromone production in Helicoverpa [correction of Hercoverpa] armigera.

The quantitative structure activity relationship (QSAR) of octopaminergic agonists responsible for the inhibition of sex-pheromone production in Helicoverpa [corrected] armigera, was analyzed using physicochemical parameters, molecular shape analysis (MSA), molecular field analysis (MFA), and receptor surface model (RSM), respectively. The dose-response studies were performed in vitro analyzing the effect of these compounds on intracellular cAMP production in the presence of pheromone biosynthesis activating neuropeptide (PBAN) at 1 pmol/intersegment. Six active derivatives were identified in the order of decreasing pheromonostatic activity: 2-(2,6-dimethylanilino)imidazolide (6) > 2-(2-methyl-4-chloroanilino)oxazolidine (1) > clonidine (5) > 2-(2,6-diethylanilino)thiazolidine (8) > 2-(3,5-dichlorobenzylamino)-2-oxazoline (4) > tolazoline (10) which were all active in the nanomolar range in inhibition of cAMP production by 1 pmol PBAN/intersegment. Four other compounds were less active having Ki in the micromolar range. An MSA was tried to obtain QSAR equation that incorporates spatial molecular similarity data of those compounds. MFA on the training set of those compounds evaluated effectively the energy between a probe and a molecular model at a series of points defined by a rectangular or spherical grid. An RSM was generated using some subset of the most active structures. Three-dimensional energetics descriptors were calculated from RSM/ligand interaction and these three-dimensional descriptors were used in QSAR analysis. These results indicate that these derivatives could provide useful information in the characterization and differentiation of octopaminergic receptor types and subtypes.

Adrenergic alpha-Agonists↗

PubMed1999

Three-dimensional pharmacophore hypotheses of octopamine receptor responsible for the inhibition of sex-pheromone production in Helicoverpa armigera.

Three-dimensional pharmacophore hypotheses were built on the basis of a set of nine octopamine (OA) agonists responsible for the inhibition of sex-pheromone production in Helicoverpa armigera. Of the 10 models generated by the program Catalyst/Hypo, hypotheses including hydrogen-bond acceptor (HBA), hydrophobic (Hp), and hydrophobic aliphatic (HpAl) features were considered important and predictive in evaluating OA agonists. An HBA and four hydrophobic features are the minimum components of an effective OA agonist-binding hypothesis, which resembles the results of binding activity to locust OAR3. Active agonists mapped well onto all of the features of the hypothesis, such as HBA, Hp, and HpAl features. On the other hand, inactive compounds lacking binding affinity were shown to be poorly capable of achieving an energetically favorable conformation shared by the active molecules in order to fit the 3D chemical feature pharmacophore models. Those hypotheses are considered useful in designing new leads for more active compounds. Further research on the comparison of models from agonists may help elucidate the mechanisms of OA receptor-ligand interactions.

Animals↗

PubMed1998

Quantitative structure-activity studies of octopaminergic agonists and antagonists against nervous system of Locusta migratoria.

The quantitative structure activity relationship (QSAR) of octopaminergic agonists and antagonists against the thoracic nerve cord of the migratory locust, Locusta migratoria L., was analyzed using physicochemical parameters and regression analysis. The hydrophobic effect, dipole moment, and shape index were important in terms of Ki: the more hydrophobic, the greater dipole moment, and the smaller shape index of the molecules, the greater the activity. A receptor surface model (RSM) was generated using some subset of the most active structures. Three-dimensional energetics descriptors were calculated from RSM/ligand interaction and these three-dimensional descriptors were used in QSAR analysis. This data set was studied further using molecular shape analysis.

Animals↗

PubMed1997

Quantitative structure-activity studies of octopaminergic 2-(arylimino)thiazolidines and oxazolidines against the nervous system of Periplaneta americana L.

The quantitative structure-activity relationship (QSAR) of octopaminergic 2-(arylimino)thiazolidines (AITs) and 2-(arylimino)oxazolidines (AIOs) against the thoracic nerve cord of the American cockroach, Periplaneta americana L., was analysed using reported physicochemical parameters and regression analysis. The more electron-donating, the less bulky at m-position, and the more hydrophobic the substituent, the greater the activity. The plots of observed log Vmax values against calculated log Vmax values having substituents on the m-position deviated downwards from those of compounds having substituents at the 0- and/or p-positions. The more hydrophobic and the more electron-withdrawing the substituent, the greater the activity. AIO with a 2, 3, 4-trichlorophenyl group (58) was more active than its thiazolidine derivative, 2-(2,3,4-trichlorophenylimino)thiazolidine (38) in terms of Vmax:Vmax of 58 was 30% relative to octopamine (OA), whereas that of 38 has been 9% relative to OA, respectively. Superimposition of energy-minimized OA and 58 revealed structural and conformational similarities that might account for the high activity of 58.

Animals↗

PubMed1996

Transdominant inhibition of Moloney murine leukemia virus proliferation by defective mutants of reverse transcriptase.

To investigate the dominant-negative inhibition of Moloney murine leukemia virus (Mo-MuLV) proliferation by polymerization-defective mutants of reverse transcriptase (RT), we constructed several plasmids harboring the Mo-MuLV RT gene in which the YVDD sequence, one of the conserved sequences in RNA-dependent polymerases, was altered, and then transformed mouse NIH3T3 cells and Escherichia coli with the mutant plasmids. Mouse NIH3T3 cells expressing these mutant RT genes were highly resistant to Mo-MuLV proliferation. The mutant RT expressed in E. coli exhibited no polymerization activity, but it retained its binding activity to the template RNA and inhibited in vitro poly(dG) synthesis occurring with the wild-type RT. These results suggest that the competition for binding of the two types of enzymes to the template is responsible for the resistance to Mo-MuLV proliferation and that the YVDD sequence of Mo-MuLV may be a good target for dominant-negative inhibition of retroviral proliferation.

3T3 Cells↗

PubMed1994

A hammerhead ribozyme inhibits the proliferation of an RNA coliphage SP in Escherichia coli.

Ribozymes are potentially powerful tools for the suppression of intracellular gene expression. However, the few reports that exist of their activities in bacteria have described mixed success. Chuat and Galibert (Chuat, J.-C., and Galibert, F. (1989) Biochem. Biophys. Res. Commun. 162, 1025-1029) failed to detect any trans-activities of hammerhead ribozymes in Escherichia coli, while Sioud and Drlica (Sioud, M., and Drlica, K. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 7303-7307) reported complete inhibition of expression of the gene for a nonbacterial protein, HIV-1 integrase, by trans-acting hammerhead ribozymes in E. coli. It is of interest to determine whether ribozymes can really be used in natural bacterial systems (Altman, S. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 10898-10900). We now report that a ribozyme designed to cleave the A2 gene of RNA coliphage SP, when transcribed from a plasmid in E. coli caused failure of the proliferation of progeny phage. Inactive ribozymes with altered catalytic sequences did not affect phage growth. These results indicate that it is mainly the catalytic activity of the ribozyme and not its function as an antisense molecule that is responsible for suppressing the proliferation of the RNA phage. Moreover, an analysis based on numbers of plaque-forming units and the function of the A2 protein indicated that antisense RNA may successfully compete with ribosomes in targeting mRNA while ribozymes in this study may not compete with ribosomes in naturally occurring bacterial transcription/translation-coupled systems.

Base Sequence↗