Embryonic Responses to Structurally Related Inhibitors

Development ◽  
1960 ◽  
Vol 8 (4) ◽  
pp. 445-456
Author(s):  
Kathe Liedke ◽  
H. B. Gillespie ◽  
Samuel Graff

Substituted benzotriazoles (Bt) have been shown to bring about interesting inhibitory effects on Rana pipiens embryos of 2-cell to tail-bud stages (Liedke, Engelman, & Graff, 1954, 1955, 1957a, 1957b). These benzotriazoles did not have selective cytotoxic effects on sensitive embryonic structures as similarly substituted benzimidazoles (Bz) and quinoxalines (Q) invariably did. The latter compounds, Bz and Q, were most active against younger stages, especially those in cleavage. On the other hand, it was found that the susceptibility to the benzotriazoles increased with age of embryo; more differentiated stages were affected most. The type of response was determined by the parent structure, but certain substituents, the nitro group in particular, appeared to enhance the magnitude of the effect. The activating effect of the nitro group was in turn modified to varying degree by an accompanying methoxy, hydroxy, or amino group.


1978 ◽  
Vol 40 (02) ◽  
pp. 377-386 ◽  
Author(s):  
Naotika Toki ◽  
Sumiyoshi Takasugi ◽  
Hiroyuki Sumi ◽  
Takuso Yamura

SummarySix different plasmins were prepared by incubating human plasminogen with various amounts of streptokinase or urokinase. It was confirmed that the six different plasmins possessed similar caseinolytic activities, and the inhibitory effects of α 1-antitrypsin on caseinolytic activities of the six different plasmins were all the same. On the other hand, interactions between the six different plasmins and α2-macroglobulin were complicated. Plasmins activated by cleavage of plasminogen were almost immediately or effectively inhibited by α2-macroglobulin. However, plasmin activated by complex formation of plasminogen with streptokinase was not so immediately or effectively inhibited by α2- macroglobulin. It was supposed that the difference between these two results on the interaction between plasmin and α2-macroglobulin might be due to the difference in molecular form of plasmin. In the present study, it was also confirmed that streptokinase or urokinase, in free form in the reaction mixture, interfered with the interaction between plasmin and α2-macroglobulin. The cause for such interference was discussed.



Zygote ◽  
2006 ◽  
Vol 14 (1) ◽  
pp. 17-22 ◽  
Author(s):  
T. Hayashi ◽  
H. Sato ◽  
H. Iwata ◽  
T. Kuwayama ◽  
Y. Monji

The present study examined the inhibitory effects of various pretreatment concentrations (0–100 μM) of the calcium ionophore A23187 on polyspermic fertilization and then examined the effect of the maturation period and the time between calcium ionophore treatment and fertilization on the inhibitory effect of calcium ionophore on polyspermic fertilization. In experiment 1, a high concentration of calcium ionophore (100 μM) increased the rate of activated oocytes, but the rate of fertilization declined. On the other hand, when oocytes were treated with a low concentration of calcium ionophore (10 μM), monospermic fertilization was significantly increased (10 μM; 31.3%) (p < 0.05). In experiment 2, oocytes were cultured for various times (0, 0.5, 3, 6 h) after calcium ionophore treatment (10 μM) before fertilization. The highest rate of monospermic fertilization was detected in the oocytes cultured for 6 h after calcium ionophore treatment before fertilization. In experiments 3 and 4, we examined the effect of the maturation period (40 h or 44 h) on the rate of fertilization and blastulation of oocytes pretreated with calcium ionophore. The treatment of oocytes with calcium ionophore significantly decreased the rate of polyspermic fertilization regardless of the maturation period (44 h: with calcium ionophore 26.25% vs without 78.8%; 40 h: with calcium ionophore 37.5% vs without 77.5%); however, calcium ionophore treatment increased the rates of monospermic fertilization and blastulation of the oocytes matured for 44 h, but not those matured for 40 h. In conclusion, activation with a low concentration of calcium ionophore (10 μM) and a further 6 h of culture before fertilization improved the rate of monospermic fertilization and blastulation.



2006 ◽  
Vol 51 (1) ◽  
pp. 175-180 ◽  
Author(s):  
Go Hirokawa ◽  
Hideko Kaji ◽  
Akira Kaji

ABSTRACT The effect of paromomycin on the interaction of ribosomal subunits was studied. Paromomycin inhibited the antiassociation activity of initiation factor 3 (IF3). Furthermore, ribosomal subunits were associated to form 70S ribosomes by paromomycin even in the presence of 1 mM Mg2+. Paromomycin did not inhibit the binding of IF3 to the 30S ribosomal subunits. On the other hand, IF3 bound to the 30S subunits was expelled by paromomycin-induced subunit association (70S formation). These results indicate that the stabilization of 70S ribosomes by paromomycin may in part be responsible for its inhibitory effects on translocation and ribosome recycling.



1967 ◽  
Vol 45 (13) ◽  
pp. 1411-1424 ◽  
Author(s):  
R. E. Moskalyk ◽  
L. G. Chatten

Sulfanilamides were found to undergo alkylation with xanthydrol, yielding either mono- or di-xanthenyl derivatives. The site of substitution, common to all sulfanilamides having a free p-amino group, was shown to be the N4-position in the sulfanilamide molecule. Three additional unique reactive sites were observed. Sulfanilamides carrying a thiazole, thiadiazole, or pyridazine substituent in the N1-position were also alkylated on the annular nitrogen atom of the heterocyclic ring, the reaction having occurred from the imido tautomeric form. Sulfisoxazole (IK), on the other hand, reacted from the amido form to give the N1,N4-dixanthenyl derivative. Sulfadimethoxine (Ih) was substituted at carbon, as well as at nitrogen, to yield N4-xanthenyl-N1-(2,6-dimethoxy-5-(9-xanthenyl)-4-pyrimidyl)sulfanilamide.Sulfanilamides possessing pKa values of about 5.5 were found to be sufficiently acidic to catalyze their own reaction with xanthydrol, and no external catalyst was necessary. The exceptional ease of formation of the xanthylium ion was postulated to be associated with the resulting stability of this carbonium ion by virtue of its acquired aromatic character.



1996 ◽  
Vol 107 (2) ◽  
pp. 261-270 ◽  
Author(s):  
G E Breitwieser ◽  
A A Altamirano ◽  
J M Russell

Bumetanide-sensitive (BS) unidirectional fluxes of (36)Cl- or (22)Na+ were measured in internally dialyzed squid giant axons while varying the intra- or extracellular concentrations of Na+ and/or Cl-. Raising either [Cl-]i or [Na+]i resulted in a concentration-dependent reduction of the BS influx of both (36)Cl- and (22)Na+. Raising [Cl-]i above 200 mM completely blocked BS influxes. However, raising [Na+]i to 290 mM resulted in saturable but incomplete inhibition of both BS Na+ influx and BS Cl- influx. The consequences of varying intracellular Cl- on cotransporter effluxes were complex. At lower [Cl-]i values (below 100 mM) intracellular Cl- activated cotransporter effluxes. Surprisingly, however, raising [Cl-]i levels &gt; 125 mM resulted in a [Cl-]i-dependent inhibition of BS effluxes of both Na+ and Cl-. On the other hand, raising [Na+]i resulted only in the activation of the BS Na+ efflux; intracellular Na+ did not inhibit BS efflux even at 290 mM. The inhibitory effects of intracellular Na+ on cotransporter-mediated influxes, and lack of inhibitory effects on BS effluxes, are consistent with the trans-side inhibition expected for an ordered binding/release model of cotransporter operation. However, the inhibitory effects of intracellular Cl- on both influxes and effluxes are not explained by such a model. These data suggest that Cl may interact with an intracellular site (or sites), which does not mediate Cl transport, but does modulate the transport activity of the Na+, K+, Cl- cotransporter.



1959 ◽  
Vol 10 (1) ◽  
pp. 1 ◽  
Author(s):  
LT Evans

The influence of various temperature and photoperiod regimes on flower initiation and flowering in eight strains of T. subterraneum has been examined, using the controlled environment facilities of the Earhart Laboratory. Flower initiation in subterranean clover appears to be under the control of three interacting partial processes, two of which are synergistic and promotive while the third is inhibitory. The promotive processes are possibly both light-independent, one being favoured by high temperatures and the other (the vernalization process) by low temperatures. The inhibitory process, on the other hand, is restricted to the diurnal dark period and is favoured by high temperatures. The interaction between the vernalization and dark inhibitory processes is such that in the absence of dark inhibition no vernalization is required by any strain, while on. the other hand sufficient vernalization can apparently overcome all dark inhibitory effects. Treatment with gibberellic acid eliminates the need for vernalization by plants of at least one early-flowering strain when. grown in short days at high temperatures. The strains of subterranean clover differ markedly in their responses to the three partial processes. In their response to the dark inhibitory process two strains are more affected by night temperature than by night length, while in two other strains the opposite is the case, which suggests that the dark inhibitory process could be resolved into more than one component.



1979 ◽  
Vol 42 (05) ◽  
pp. 1398-1410
Author(s):  
A J Osbahr

SummaryFibrinogen is polymerized by a number of group specific reagents including diazomethane, thionyl chloride and di-methyl sulfate at pH 7.4. The relationship between the number of methyl groups incorporated into fibrinogen and the extent of polymerization was evaluated. With diazomethane and thionyl chloride as modifying agents, polymerization ensued in approximately IV2 hr with extensive modification of fibrinogen. On the other hand, m�thylation via di-methyl sulfate-induced polymer formation occurs in approximately 35 min with primarily carboxylic acid group esterification. The polymerized fibrinogen formed under these conditions exhibited properties that were closely similar with the physiological fibrin clot.Amino group determinations revealed the m�thylation of amino acid residues other than the expected esterification of carboxylic acid groups. Diazomethane induced both N- methylation of lysine, as well as O-methylation of tyrosine, as estimated from spectrophotometric analysis. On the other hand, thionyl chloride modified only a small number of amino groups, and di-methyl sulfate modification resulted in no significant amounts of amino group methylation during the process of modification induced polymerization of fibrinogen.The profile of the number of methoxyl groups incorporated into fibrinogen with time for diazomethane modification may reflect a conformational change in the protein due to a more nonspecific m�thylation. Both the reagent and the conditions of modification were found to be important in achieving a selective modification of fibrinogen.A possible interpretation of these results is the esterification of carboxylic acid groups in the fibrinogen with reduction in the prevailing carboxylate ion negative repulsion, thereby achieving an increased protein-protein interaction with a resulting polymerization.



1991 ◽  
Vol 65 (6) ◽  
pp. 1567-1579 ◽  
Author(s):  
D. X. Zhang ◽  
C. M. Owens ◽  
W. D. Willis

1. Recordings were made from the lumbosacral spinal cord in anesthetized macaque monkeys. The inhibitory effects of electrical stimulation of the periaqueductal gray (PAG) and the cerebral cortex or cerebral peduncle (CP) were tested and compared by recording 1) cord dorsum potentials evoked by stimulation of the sural nerve, 2) discharges recorded extracellularly, and 3) membrane potentials recorded intracellularly from spinothalamic tract (STT) neurons at rest (background activity) or in response to stimulation of the sural nerve. 2. Stimulation of the cortex or in the CP preferentially reduced the amplitude of the N1 and N2 waves of the cord dorsum potential evoked by stimulation of the sural nerve, without affecting the N3 wave. Stimulation of the PAG, on the other hand, reduced the amplitude of the N3 wave with little effect on the N1 and N2 waves. 3. The activity of 62 STT neurons was recorded extracellularly. Stimulation of the PAG or the cortex/CP inhibited nonpreferentially the responses of the neurons in the superficial laminae to all afferent inputs. On the other hand, stimulation of the PAG or the cortex/CP inhibited preferentially the responses of most STT neurons in deep layers of the dorsal horn to the small or large afferent input, respectively. 4. Thirty-five neurons were recorded intracellularly. The membrane potential of the neurons averaged -45.5 +/- 10.1 (SD) mV. All neurons were recorded in laminae III-VI; the neurons were of the wide-dynamic-range (WDR) type and had background activity. 5. The inhibitory effects of stimulation of the PAG were tested on all 35 neurons. In 32 of the neurons, stimulation of the PAG evoked a hyperpolarization. The background activity of the neurons was reduced (generally it completely ceased) by the hyperpolarization. In three neurons stimulation of the PAG did not evoke a hyperpolarization and the background activity of the neurons did not change. Nevertheless, the responses of these three neurons to afferent input were inhibited by stimulation in the PAG. 6. The inhibitory effects of stimulating the cortex and/or the CP were tested in 26 of the 35 neurons. Stimulation of the cortex and/or the CP evoked a hyperpolarization in all the neurons, although, in 10 of the 26 neurons, stimulation of the CP also evoked a depolarization. The hyperpolarization generally blocked the background activity of the neurons. 7. The effective stimuli in the PAG and the cortex/CP to evoke a hyperpolarization in STT neurons were short, high-frequency trains of pulses.(ABSTRACT TRUNCATED AT 400 WORDS)



1986 ◽  
Vol 251 (1) ◽  
pp. C1-C9 ◽  
Author(s):  
P. A. Knauf ◽  
N. A. Mann

Experiments were performed with intact human red blood cells to determine whether the inhibitory effects of high Cl- concentrations on Cl- exchange are primarily due to interaction at the cytoplasmic or the external surface of the membrane. When internal Cl- was varied from 150 mM to 600 mM Cl- (using the nystatin technique), keeping external Cl- constant at 150 mM (with sucrose added to maintain osmotic balance), Cl- exchange was inhibited almost exactly as much as when both internal and external Cl- were increased from 150 mM to 600 mM. On the other hand, if internal Cl- was maintained constant at 600 mM, variation of external Cl- (with either sucrose, gluconate, or citrate-sucrose mixtures replacing Cl-) had no consistent effect on Cl- exchange. Even if internal Cl- was kept at 150 mM by substitution of gluconate for Cl-, an increase in external Cl- from 150 mM to 600 mM did not significantly inhibit Cl- exchange. Thus the self-inhibitory effects of Cl- seem to be caused primarily by binding to a site at the cytoplasmic side of the membrane. External Br-, on the other hand, did cause a significant inhibition of Cl- exchange. In contrast to the inhibitory effects of Cl- at neutral pH, at very high pH (around pH 11) there is an activation of Cl- exchange at very high Cl- concentrations. This effect, however, depends on binding of Cl- to an external site. Thus there seem to be at least two different low-affinity Cl- binding sites, one at the cytoplasmic side, which inhibits Cl- exchange, and one at the external side, which activates Cl- exchange at high external pH.



OENO One ◽  
2000 ◽  
Vol 34 (4) ◽  
pp. 145
Author(s):  
Béchir Ezzili ◽  
M. Bejaoui

<p style="text-align: justify;">Investigation of the Tunisian vineyard showed that on long canes of Muscatel of Italy, a certain percent of growing branches presents both the acrotony and basitony phenomena. The discussion of the investigation results allowed us to define a new hypothesis according to which these phenomena are controlled in part by a hormonal balance. In order to test this hypothesis, we are proceeded by studying the influence of growth regulators on bud bursting carried on one eye cuttings in one hand and on long canes to 10 units cultivated in greenhouse and in the laboratory on the other hand as well as on long wood in the vineyard. We report in this work the results relative to one eye cuttings. We applied an immersion of buds carried by one eye cuttings and in phase of post-dormancy, during 24 hours in different growth regulators at different concentrations (GA3 50 mg/l, 25 mg/l, 12.5 mg/l; ABA 25 mg/l, 12.5 mg/l, 6.25 mg/l; 6BAP 50 mg/l, 25 mg/l, 12.5 mg/l; Kinétin 50 mg/l, 25 mg/l, 12.5 mg/l; AIA, AIB, ANA 50 mg/l, 25 mg/l, 12.5 mg/l; 2-4D 10 mg/l, 5 mg/l, 2.5 mg/l). Results of these treatments show that there are generally some inhibitory effects for gibberellins and auxins. In the contrary, cytokinins possess the stimulate effects of bud bursting, applied during the end of the post dormancy phase.</p><p style="text-align: justify;">The interesting conclusion concerning the interaction of two growth regulators resides especially in the interaction cytokinin-auxins. According to our results auxins possess some inhibitory effects on the bud bursting, on the contrary, cytokinins possess a stimulate effect. The Interaction cytokinin-auxin seems to attenuate the negative effect of auxins on the bud bursting. We will see subsequently that differed applications of these regulators can give a clear demonstration.</p>



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