scholarly journals Excitation, adaption, and deadaptation of the cAMP-mediated cGMP Response in dictyostelium discoideum

1983 ◽  
Vol 96 (2) ◽  
pp. 347-353 ◽  
Author(s):  
PJM Van Haaster ◽  
PR Van Der Heijden
Keyword(s):  
Cell Suspension ◽  
Dictyostelium Discoideum ◽  
Half Life ◽  
Cell Aggregation ◽  
First Order ◽  
Intracellular Cgmp ◽  
First Order Kinetics ◽  
A Cell ◽  
Stimulation Period ◽  
Extracellular Camp

Extracellular cAMP induces chemotaxis and cell aggregation in dictyostelium discoideum cells. cAMP added to a cell suspension is rapidly hydrolyzed (half-life of 10 s) and induces a rapid increase of intracellular cGMP levels, which reach a peak at 10 s and recover prestimulated levels at about 30 s. This recovery is not due to removal of the stimulus because the nonhydrolyzable analogue adenosine 3',5'-monophosphorothioate-Sp- stereoisomer (cAMPS) induced a comparable cGMP response, which peaked at 10 s, even at subsaturating cAMPS concentrations. When cells were stimulated twice with the same cAMP concentration at a 30-s interval, only the first stimulus produced a cGMP response. Cells did respond to the second stimulus when the concentration of the second stimulus was higher than that of the first stimulus. By increasing the interval between two identical stimuli, the response to the second stimulus gradually increased. Recovery from the first stimulus showed first-order kinetics with a half-life of 1-2 min. The stimulation period was shortened by adding phosphodieterase to the cell suspension. The cGMP response was unaltered if the half-life of cAMP was reduced to 2 S. The peak of the transient cGMP accumulation still appeared at 10 s even when the half- life of cAMP was 0.4 s; however, the height of the cGMP peak was reduced. The cGMP response at 10 s after stimulation was diminished by 50 percent when the half-life of 10(-7) M cAMP was 0.5 s or when the half-life of 10(-8) M cAMP was 3.0 s. These results show that the cAMP signal is transduced to two opposing processes: excitation and adaptation. Within 10 s after addition of cAMP to a cell suspension the level of adaptation reaches the level of excitation, which causes the extinction of the transduction of the signal. Deadaptation starts as soon as the signal is removed, and it has first-order kinetics with a half-life of 1-2 min.

In-vitro Kinetic Hydrolysis Study of Metronidazole Derivatives with Carvacrol and Eugenol Using Validated RP-HPLC Method

2020 ◽  
Vol 16 ◽  
Author(s):  
M. Alarjah
Keyword(s):  
Half Life ◽  
Hplc Method ◽  
Hydrolysis Rate ◽  
First Order ◽  
First Order Kinetics ◽  
Rp Hplc ◽  
Pharmacokinetic Properties ◽  
Pseudo First Order ◽  
Kinetic Hydrolysis

Background: Prodrugs principle is widely used to improve the pharmacological and pharmacokinetic properties of some active drugs. Much effort was made to develop metronidazole prodrugs to enhance antibacterial activity and or to improve pharmacokinetic properties of the molecule or to lower the adverse effects of metronidazole. Objective: In this work, the pharmacokinetic properties of some of monoterpenes and eugenol pro metronidazole molecules that were developed earlier were evaluated in-vitro. The kinetic hydrolysis rate constants and half-life time estimation of the new metronidazole derivatives were calculated using the validated RP-HPLC method. Method: Chromatographic analysis was done using Zorbbax Eclipse eXtra Dense Bonding (XDB)-C18 column of dimensions (250 mm, 4.6 mm, 5 μm), at ambient column temperature. The mobile phase was a mixture of sodium dihydrogen phosphate buffer of pH 4.5 and methanol in gradient elution, at 1ml/min flow rate. The method was fully validated according to the International Council for Harmonization (ICH) guidelines. The hydrolysis process carried out in an acidic buffer pH 1.2 and in an alkaline buffer pH 7.4 in a thermostatic bath at 37ºC. Results: The results followed pseudo-first-order kinetics. All metronidazole prodrugs were stable in the acidic pH, while they were hydrolysed in the alkaline buffer within a few hours (6-8 hr). The rate constant and half-life values were calculated, and their values were found to be 0.082- 0.117 hr-1 and 5.9- 8.5 hr., respectively. Conclusion: The developed method was accurate, sensitive, and selective for the prodrugs. For most of the prodrugs, the hydrolysis followed pseudo-first-order kinetics; the method might be utilised to conduct an in-vivo study for the metronidazole derivatives with monoterpenes and eugenol.

Use of purified lyophilized human lactate dehydrogenase isoenzyme 5 in a study of measuring lactate dehydrogenase activity.

1989 ◽  
Vol 35 (8) ◽  
pp. 1774-1776 ◽  
Author(s):  
D A Smith ◽  
G C Moses ◽  
A R Henderson
Keyword(s):  
Lactate Dehydrogenase ◽  
Half Life ◽  
Specific Activity ◽  
Lactate Dehydrogenase Activity ◽  
Bovine Albumin ◽  
First Order ◽  
First Order Kinetics ◽  
The Stability ◽  
Lactate Dehydrogenase Isoenzymes ◽  
Excellent Stability

Abstract We examined the stability of human lactate dehydrogenase (EC 1.1.1.27) isoenzyme 5--purified to a specific activity of about 400 kU/g--when lyophilized in a buffered, stabilized matrix of bovine albumin. This isoenzyme was prepared with a final activity of about 500 U/L and stored at -20, 4, 20, 37, and 56 degrees C for as long as six months. This isoenzyme decayed with approximate first-order kinetics, with an estimated half-life at -20 degrees C of about 475 years. Stability of reconstituted samples stored at 20 or 4 degrees C was poor, suggesting that the reconstituted material should be used without delay; material stored at -20 degrees C showed excellent stability for 15 days. We propose that such preparations might be further investigated as standards for use in electrophoresis of lactate dehydrogenase isoenzymes.

scholarly journals Soil Persistence of Diuron Applied to Cotton Cultivation in Red and Black Soils

2020 ◽  
pp. 50-57
Author(s):  
Md. Mifta Faizullah ◽  
T. Ramprakash ◽  
T. Anjaiah ◽  
M. Madhavi
Keyword(s):  
Half Life ◽  
Field Experiments ◽  
Black Soil ◽  
Red Soil ◽  
First Order ◽  
First Order Kinetics ◽  
Soil Persistence ◽  
Red Soils ◽  
Top Soil ◽  
Telangana State

Persistence of diuron applied to cotton as preemergence spray at varied rates of application (0.5, 0.75, 1.0 kg ha-1) was studied in field experiments conducted simultaneously in red and black soils at Professor Jayashankar Telangana State Agricultural University, Rajendranagar during kharif, 2018. In both red and black soils, persistence of diuron was observed beyond 120 days after application and the concentration of diuron in the top soil (0-15 cm) was higher in black soils compared to red soils from 0 Days to 120 Days. Higher dose of diuron showed greater soil persistence in both red and black soil. Diuron dissipation in soil followed first order kinetics in both the soils. Field half life of diuron was higher in black soil was 53.3-77.0 days at different rates of application than in red soil (53.3-69.3 days).

A Human Pharmacological Study Comparing Conventional Heparin and a Low Molecular Weight Heparin Fragment

1985 ◽  
Vol 53 (02) ◽  
pp. 208-211 ◽  
Author(s):  
G Bratt ◽  
E Törnebohm ◽  
D Lockner ◽  
G Bergströ
Keyword(s):  
Molecular Weight ◽  
Half Life ◽  
Low Molecular Weight Heparin ◽  
Pharmacological Study ◽  
Low Molecular Weight ◽  
Dose Dependency ◽  
First Order ◽  
First Order Kinetics ◽  
Heparin Activity ◽  
Different Doses

SummaryThe pharmacokinetics of a heparin fragment of low molecular weight (LMWH) of 4000-5000 D and unfractioned standard heparin (UFH) have been studied after i. v. injections of different doses and infusions in 8 humans.The heparin activity was significantly higher and the effect on APTT lower after LMWH fragment as compared to UFH in the same doses.The half-life of heparin activity was about 1 hr for UFH and about 2 hr for LMWH. LMWH was found to be eliminated according to first order kinetics and there were no signs of dose dependency.

Role of pH on Metribuzin Dissipation in Field Soils

Weed Science ◽  
1976 ◽  
Vol 24 (5) ◽  
pp. 508-511 ◽  
Author(s):  
James S. Ladlie ◽  
William F. Meggitt ◽  
Donald Penner
Keyword(s):  
Soil Ph ◽  
Half Life ◽  
Residue Analysis ◽  
Soil Samples ◽  
First Order ◽  
First Order Kinetics ◽  
Field Soils ◽  
Pseudo First Order

Metribuzin [4-amino-6-tert-butyl-3-(methylthio)-as-triazine-5(4H)one] residue analysis of soil samples showed greater amounts of residue extractable at soil pH 6.7 than 4.6. Metribuzin leaching increased with increasing soil pH. Metribuzin disappearance from soil followed pseudo first-order kinetics. The half-life of metribuzin decreased as soil pH increased and increased at all soil pH levels as depth of sampling increased. The decreased activity and decreased rate of metribuzin dissipation at lower soil pH is apparently due to protonation and increased adsorption.

scholarly journals Equations describing the effects of the transient stability of subpopulations of nascent hnRNAs on the kinetics of turnover of hnRNA

1986 ◽  
Vol 233 (3) ◽  
pp. 905-908
Author(s):  
K C Kleene
Keyword(s):  
Half Life ◽  
Transient Stability ◽  
Precise Description ◽  
Electron Microscopic ◽  
First Order ◽  
First Order Kinetics ◽  
Microscopic Studies ◽  
Rate Of Decay ◽  
Kinetics Of ◽  
Continuous Labelling

The equations that have been used previously to analyse the rate of decay of hnRNA implicitly assume that nascent hnRNAs are degraded stochastically. This assumption is inconsistent with electron-microscopic studies of transcription cited here, which show that nascent hnRNAs are not degraded during transcription, implying that hnRNA degradation occurs only after termination of transcription and release of the hnRNA from chromatin. Equations are derived describing the accumulation of radioactivity hnRNA during continuous labelling assuming that nascent hnRNAs are stable and that hnRNAs decay with first-order kinetics only after completion of transcription. The effects of the transient stability of nascent hnRNAs on the kinetics of hnRNA turnover can become important when the half-life of the hnRNA is shorter than the time to transcribe an hnRNA from the point of initiation to the point of termination. These equations should prove useful in studies of hnRNA turnover that require a precise description of the labelling kinetics of nascent and completed subpopulations of hnRNA.

scholarly journals Effect of Sunlight and Ultraviolet Light on Dissipation of Fipronil Insecticide in Two Soils and Effect of pH on its Persistence in Aqueous Medium

2014 ◽  
Vol 7 ◽  
pp. ASWR.S14847 ◽  
Author(s):  
Ankita Verma ◽  
Anjana Srivastava ◽  
Shailendra Singh Chauhan ◽  
Prakash Chandra Srivastava
Keyword(s):  
Aqueous Medium ◽  
Half Life ◽  
Uv Light ◽  
Light Exposure ◽  
Clay Loam ◽  
Sandy Clay Loam ◽  
First Order ◽  
First Order Kinetics ◽  
Sandy Clay ◽  
Uv Lamp

In a laboratory investigation, the effect of natural sunlight and UV light exposure on dissipation of fipronil insecticide from two soils (clay loam and sandy clay loam) and the effect of pH on the persistence of fipronil in aqueous medium were studied. Dissipation of fipronil insecticide under sunlight followed biphasic first order kinetics in both soils. The half-life of the insecticide in sandy clay loam type soil was found to be 5.71 days for the first faster phase and 23.88 days for the second slower phase, whereas, in clay loam soil, the corresponding half-lives were 4.02 and 8.38 days, respectively. Under the UV light exposure, the dissipation of fipronil followed a single phase first order kinetics in both the soils with a half-life of 3.77 days in clay loam and 5.37 days in sandy clay loam, respectively. Residues of fipronil dissipated faster in clay loam than in sandy clay loam under both sunlight and UV lamp light. As compared to sunlight, dissipation was found to be faster under UV lamp light. Persistence of fipronil in aqueous medium under different pH conditions revealed that fipronil residues were below the limit of detection (LOD), <0.05 μg g−1, after 40 days of sampling at all the three pH. The dissipation of fipronil from aqueous medium increased with increasing pH from 5.0 to 9.0; the corresponding half-lives were 14.12, 9.83, and 6.76 days at pH 5.0, 7.0, and 9.0, respectively.

scholarly journals Seven Dictyostelium discoideum phosphodiesterases degrade three pools of cAMP and cGMP

2007 ◽  
Vol 402 (1) ◽  
pp. 153-161 ◽  
Author(s):  
Sonya Bader ◽  
Arjan Kortholt ◽  
Peter J. M. Van Haastert
Keyword(s):  
Dictyostelium Discoideum ◽  
Cyclic Nucleotide ◽  
Class Ii ◽  
Class I ◽  
Intracellular Camp ◽  
Specific Class ◽  
High Affinity ◽  
Intracellular Cgmp ◽  
Rare Class ◽  
Extracellular Camp

The Dictyostelium discoideum genome uncovers seven cyclic nucleotide PDEs (phosphodiesterases), of which six have been characterized previously and the seventh is characterized in the present paper. Three enzymes belong to the ubiquitous class I PDEs, common in all eukaryotes, whereas four enzymes belong to the rare class II PDEs that are present in bacteria and lower eukaryotes. Since all D. discoideum PDEs are now characterized we have calculated the contribution of each enzyme in the degradation of the three important pools of cyclic nucleotides: (i) extracellular cAMP that induces chemotaxis during aggregation and differentiation in slugs; (ii) intracellular cAMP that mediates development; and (iii) intracellular cGMP that mediates chemotaxis. It appears that each cyclic nucleotide pool is degraded by a combination of enzymes that have different affinities, allowing a broad range of substrate concentrations to be degraded with first-order kinetics. Extracellular cAMP is degraded predominantly by the class II high-affinity enzyme DdPDE1 and its close homologue DdPDE7, and in the multicellular stage also by the low-affinity transmembrane class I enzyme DdPDE4. Intracellular cAMP is degraded by the DdPDE2, a class I enzyme regulated by histidine kinase/phospho-relay, and by the cAMP-/cGMP-stimulated class II DdPDE6. Finally, basal intracellular cGMP is degraded predominantly by the high-affinity class I DdPDE3, while the elevated cGMP levels that arise after receptor stimulation are degraded predominantly by a cGMP-stimulated cGMP-specific class II DdPDE5. The analysis shows that the combination of enzymes is tuned to keep the concentration and lifetime of the substrate within a functional range.

Pharmacokinetics of verapamil in overdose

1997 ◽  
Vol 16 (1) ◽  
pp. 35-37 ◽  
Author(s):  
Kari T Kivistö ◽  
Pertti J Neuvonen ◽  
Leo Tarssanen
Keyword(s):  
Half Life ◽  
Free Fraction ◽  
Acute Poisoning ◽  
First Order ◽  
First Order Kinetics ◽  
Severe Bradycardia ◽  
Apparent Concentration ◽  
Therapeutic Measures ◽  
Total Concentrations

The information on the pharmacokinetics of verapamil in overdose is scanty. We report two adults who ingested 3.2 g and 4 g ofverapamil, respectively. Both patients had hypotension and a severe bradycardia. The highest plasma verapamil concentration in these patients was about 2200 ng/ml and 2700 ng/ml, respectively. The decline in plasma verapamil and norverapamil concen trations followed first-order kinetics, and the half-life of verapamil was 7.8 h and 15.1 h, respectively. The free fraction of verapamil (non-protein bound) was higher at total concentrations exceeding 2000 ng/ml (12 -15%) than at lower concentrations (2-6%). There seems to be no marked saturation ofthe metabolism of verapamil in acute poisoning. The apparent concentration-dependent changes in the free fraction may be due to therapeutic measures.

Sign in / Sign up

Export Citation Format

Share Document