Metabolism and cardiovascular effects of leukotrienes in warm- and cold-acclimated American bullfrogs (Rana catesbeiana)

1991 ◽  
Vol 260 (5) ◽  
pp. R834-R838
Author(s):  
C. A. Herman ◽  
G. A. Charlton ◽  
R. L. Cranfill
Keyword(s):  
Time Course ◽  
Rana Catesbeiana ◽  
Cardiovascular Effects ◽  
Leukotriene C4 ◽  
Gamma Glutamyl Transpeptidase ◽  
Leukotriene D4 ◽  
Inactivation Mechanism ◽  
Glutamyl Transpeptidase

Sulfidopeptide leukotrienes are important mediators in mammals, but much less is known of their metabolism and action in nonmammalian vertebrates. This study examines the cardiovascular effects of leukotrienes on blood pressure and heart rate and compares the metabolism of leukotrienes in vivo and in vitro in warm- and cold-acclimated bullfrogs. Leukotriene C4 (LTC4) is more potent than leukotriene D4 (LTD4) and leukotriene E4 (LTE4) in eliciting hypotension. The leukotrienes are more potent in warm-acclimated animals. Conversion of [3H]LTC4 to [3H]LTD4 occurs rapidly in warm-acclimated bullfrogs, with 15.2 +/- 1.7% of the [3H]LTC4 remaining at 1.5 min. Conversion is slower in vivo in cold-acclimated frogs, with 20.2 +/- 1.7% of the [3H]LTC4 remaining by 6 min. In blood taken from warm-acclimated frogs, conversion of [3H]LTC4 to [3H]LTD4 occurs more rapidly at 22 than at 5 degrees C. This pattern is similar in blood taken from cold-acclimated frogs, suggesting that no modification of gamma-glutamyl transpeptidase occurs at low temperature. [3H]LTE4 production is not observed in vivo or in vitro during the time course of the experiments. The rapid metabolism of LTC4 to LTD4 may represent an inactivation mechanism in amphibians. The cardiovascular effects of LTC4 in vivo may be much greater than current measurements indicate because of rapid conversion of LTC4 to the less potent LTD4.

Acetazolamide and renal ammoniagenesis

1978 ◽  
Vol 234 (3) ◽  
pp. F235-F237 ◽  
Author(s):  
S. K. Chapman ◽  
M. S. Hoover
Keyword(s):  
Ammonium Excretion ◽  
Gamma Glutamyl Transpeptidase ◽  
Gamma Glutamyl ◽  
Enzyme Systems ◽  
Glutamyl Transpeptidase

The effect of acetazolamide on ammonia-producing enzyme systems was determined in vitro at concentrations comparable to those which have been shown to abolish ammonium excretion in vivo. No change in the activity of glutaminase or gamma-glutamyl transpeptidase could be observed at concentrations up to 0.2 mM acetazolamide, and concentrations up to 1 mM were without effect on D-glutamyltransferase activity. Therefore, the effect of acetazolamide to abolish ammonium excretion cannot be explained by an action of the drug to inhibit ammoniagenesis.

Cardiovascular effects of N-methyl leukotriene C4, a nonmetabolizable leukotriene C4 analogue, and the antagonism of leukotriene-induced hypotension by Ro 23-3544, in the American bullfrog, Rana catesbeiana

1995 ◽  
Vol 73 (3) ◽  
pp. 383-389 ◽  
Author(s):  
Jimin Sun ◽  
Cell A. Herman
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Rana Catesbeiana ◽  
Cardiovascular Effects ◽  
Hypotensive Effect ◽  
Leukotriene C4 ◽  
Response Curves ◽  
Potent Effect ◽  
Leukotriene Antagonist

Although some leukotriene antagonists have been reported to block leukotriene (LT) C4 responses in vivo, it is difficult to determine whether those antagonists block the effect of LTC4 directly or act via blocking the action of LTD4, as LTC4 is metabolized to LTD4 rapidly in vivo. In this study, the dose–response curves of N-methyl LTC4 (NMLTC4), the nonmetabolizable LTC4 analogue, and the peptidoleukotrienes (LTC4, LTD4, and LTE4) were obtained in the absence and presence of the leukotriene antagonist Ro 23-3544 in cannulated frogs. The more potent effect of NMLTC4 suggests that receptors that preferentially bind LTC4 exist in frog vascular smooth muscle and the previously reported LTC4 effect is a combination of LTC4 and its less potent metabolite LTD4. The NMLTC4- and LTC4-induced hypotensive effects were antagonized by Ro 23-3544. Ro 23-3544 also antagonized the effects induced by high doses of LTD4 and LTE4. Ro 23-3544 had no effect on duration of response and did not affect heart rate responses to LTC4 at low dose of the antagonist. The data suggest that receptors that preferentially bind LTC4 in bullfrog vascular smooth muscle regulate the hypotensive effect and that they can be antagonized by Ro 23-3544.Key words: leukotriene receptors, N-methyl LTC4, Ro 23-3544, cardiovascular, bullfrog.

Comparison of High Purity Factor IX Concentrates and a Prothrombin Complex Concentrate in a Canine Model of Thrombogenicity

1991 ◽  
Vol 66 (05) ◽  
pp. 609-613 ◽  
Author(s):  
I R MacGregor ◽  
J M Ferguson ◽  
L F McLaughlin ◽  
T Burnouf ◽  
C V Prowse
Keyword(s):  
High Purity ◽  
Time Course ◽  
Prothrombin Complex Concentrate ◽  
Degradation Products ◽  
Canine Model ◽  
Factor Ix ◽  
In Vitro Tests ◽  
Albumin Infusion

SummaryA non-stasis canine model of thrombogenicity has been used to evaluate batches of high purity factor IX concentrates from 4 manufacturers and a conventional prothrombin complex concentrate (PCC). Platelets, activated partial thromboplastin time (APTT), fibrinogen, fibrin(ogen) degradation products and fibrinopeptide A (FPA) were monitored before and after infusion of concentrate. Changes in FPA were found to be the most sensitive and reproducible indicator of thrombogenicity after infusion of batches of the PCC at doses of between 60 and 180 IU/kg, with a dose related delayed increase in FPA occurring. Total FPA generated after 100-120 IU/kg of 3 batches of PCC over the 3 h time course was 9-12 times that generated after albumin infusion. In contrast the amounts of FPA generated after 200 IU/kg of the 4 high purity factor IX products were in all cases similar to albumin infusion. It was noted that some batches of high purity concentrates had short NAPTTs indicating that current in vitro tests for potential thrombogenicity may be misleading in predicting the effects of these concentrates in vivo.

Studies on the mechanism of acute inhibition of thyroglobulin hydrolysis by iodine

1985 ◽  
Vol 108 (4) ◽  
pp. 511-517 ◽  
Author(s):  
Nandalal Bagchi ◽  
Birdie Shivers ◽  
Thomas R. Brown
Keyword(s):  
Time Course ◽  
Period 2 ◽  
Iodotyrosine Deiodinase ◽  
Rate Of Hydrolysis ◽  
Underlying Mechanisms ◽  
Excess Iodide ◽  
Sites Of Action ◽  
Hydrolysis Of

Abstract. Iodine in excess is known to acutely inhibit thyroidal secretion. In the present study we have characterized the time course of the iodine effect in vitro and investigated the underlying mechanisms. Labelled thyroid glands were cultured in vitro in medium containing mononitrotyrosine, an inhibitor of iodotyrosine deiodinase. The rate of hydrolysis of labelled thyroglobulin was measured as the proportion of labelled iodotyrosines and iodothyronines recovered at the end of culture and was used as an index of thyroidal secretion. Thyrotrophin (TSH) administered in vivo acutely stimulated the rate of thyroglobulin hydrolysis. Addition of Nal to the culture medium acutely inhibited both basal and TSH-stimulated thyroglobulin hydrolysis. The effect of iodide was demonstrable after 2 h, maximal after 6 h and was not reversible upon removal of iodide. Iodide abolished the dibutyryl cAMP induced stimulation of thyroglobulin hydrolysis. Iodide required organic binding of iodine for its effect but new protein or RNA synthesis was not necessary. The inhibitory effects of iodide and lysosomotrophic agents such as NH4C1 and chloroquin on thyroglobulin hydrolysis were additive suggesting different sites of action. Iodide added in vitro altered the distribution of label in prelabelled thyroglobulin in a way that suggested increased coupling in the thyroglobulin molecule. These data indicate that 1) the iodide effect occurs progressively over a 6 h period, 2) continued presence of iodide is not necessary once the inhibition is established, 3) iodide exerts its action primarily at a post cAMP, prelysosomal site and 4) the effect requires organic binding of iodine, but not new RNA or protein synthesis. Our data are consistent with the hypothesis that excess iodide acutely inhibits thyroglobulin hydrolysis by increasing the resistance of thyroglobulin to proteolytic degradation through increased iodination and coupling.

scholarly journals Uptake and Distribution of Administered Bone Marrow Mesenchymal Stem Cell Extracellular Vesicles in Retina

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 730
Author(s):  
Biji Mathew ◽  
Leianne A. Torres ◽  
Lorea Gamboa Gamboa Acha ◽  
Sophie Tran ◽  
Alice Liu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Extracellular Vesicles ◽  
Time Course ◽  
Ganglion Cells ◽  
Ex Vivo ◽  
Dependent Manner ◽  
Paracrine Effects

Cell replacement therapy using mesenchymal (MSC) and other stem cells has been evaluated for diabetic retinopathy and glaucoma. This approach has significant limitations, including few cells integrated, aberrant growth, and surgical complications. Mesenchymal Stem Cell Exosomes/Extracellular Vesicles (MSC EVs), which include exosomes and microvesicles, are an emerging alternative, promoting immunomodulation, repair, and regeneration by mediating MSC’s paracrine effects. For the clinical translation of EV therapy, it is important to determine the cellular destination and time course of EV uptake in the retina following administration. Here, we tested the cellular fate of EVs using in vivo rat retinas, ex vivo retinal explant, and primary retinal cells. Intravitreally administered fluorescent EVs were rapidly cleared from the vitreous. Retinal ganglion cells (RGCs) had maximal EV fluorescence at 14 days post administration, and microglia at 7 days. Both in vivo and in the explant model, most EVs were no deeper than the inner nuclear layer. Retinal astrocytes, microglia, and mixed neurons in vitro endocytosed EVs in a dose-dependent manner. Thus, our results indicate that intravitreal EVs are suited for the treatment of retinal diseases affecting the inner retina. Modification of the EV surface should be considered for maintaining EVs in the vitreous for prolonged delivery.

Synthesis and turnover of proteins and mRNA in germinating wheat embryos

1982 ◽  
Vol 60 (3) ◽  
pp. 389-397 ◽  
Author(s):  
Zbyszko F. Grzelczak ◽  
Mark H. Sattolo ◽  
Linda K. Hanley-Bowdoin ◽  
Theresa D. Kennedy ◽  
Byron G. Lane
Keyword(s):  
Growth Phase ◽  
Time Course ◽  
Phase 1 ◽  
Major Product ◽  
Lag Phase ◽  
Wheat Embryo ◽  
Phase Development ◽  
Wheat Embryos

The most prominent methionine-labeled protein made when cell-free systems are programmed with bulk mRNA from dry wheat embryos has been identified with what may be the most abundant protein in dry wheat embryos. The protein has been brought to purity and has a distinctive amino acid composition, Gly and Glx accounting for almost 40% of the total amino acids. Designated E because of its conspicuous association with early imbibition of dry wheat embryos, the protein and its mRNA are abundant during the "early" phase (0–1 h) of postimbibition development, and easily detected during "lag" phase (1–5 h), but they are almost totally degraded soon after entry into the "growth" phase of development, by about 10 h postimbibition.The most prominent methionine-labeled protein peculiar to the cell-free translational capacity of bulk mRNA from "growth" phase embryos is not detected as a product of in vivo synthesis. Its electrophoretic properties and its time course of emergence, after 5 h postimbibition development, suggest that this major product of cell-free synthesis may be an in vitro counterpart to a prominent methionine-labeled protein made only in vivo, by "growth" phase embryos. Designated G because of its conspicuous association with "growth" phase development, the cell-free product does not comigrate with any prominent dye-stained band in electrophoretic distributions of wheat proteins. The suspected cellular counterpart to G, also, does not comigrate with a prominent dye-stained wheat protein during electrophoresis, and although found in particulate as well as soluble fractions of wheat embryo homogenates it is not concentrated in either nuclei or mitochondria, as isolated.

scholarly journals Temporal transcriptomic profiling reveals dynamic changes in gene expression of Xenopus animal cap upon activin treatment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yumeko Satou-Kobayashi ◽  
Jun-Dal Kim ◽  
Akiyoshi Fukamizu ◽  
Makoto Asashima
Keyword(s):  
Time Course ◽  
Transforming Growth Factor ◽  
Transcriptome Profiling ◽  
Transforming Growth Factor Β ◽  
Activin A ◽  
Cytokine Signaling ◽  
Molecular Characteristics ◽  
Transcriptional Dynamics

AbstractActivin, a member of the transforming growth factor-β (TGF-β) superfamily of proteins, induces various tissues from the amphibian presumptive ectoderm, called animal cap explants (ACs) in vitro. However, it remains unclear how and to what extent the resulting cells recapitulate in vivo development. To comprehensively understand whether the molecular dynamics during activin-induced ACs differentiation reflect the normal development, we performed time-course transcriptome profiling of Xenopus ACs treated with 50 ng/mL of activin A, which predominantly induced dorsal mesoderm. The number of differentially expressed genes (DEGs) in response to activin A increased over time, and totally 9857 upregulated and 6663 downregulated DEGs were detected. 1861 common upregulated DEGs among all Post_activin samples included several Spemann’s organizer genes. In addition, the temporal transcriptomes were clearly classified into four distinct groups in correspondence with specific features, reflecting stepwise differentiation into mesoderm derivatives, and a decline in the regulation of nuclear envelop and golgi. From the set of early responsive genes, we also identified the suppressor of cytokine signaling 3 (socs3) as a novel activin A-inducible gene. Our transcriptome data provide a framework to elucidate the transcriptional dynamics of activin-driven AC differentiation, reflecting the molecular characteristics of early normal embryogenesis.

Protein-tyrosine phosphatase activity of CD45 is activated by sequential phosphorylation by two kinases

1994 ◽  
Vol 14 (8) ◽  
pp. 5523-5532
Author(s):  
D R Stover ◽  
K A Walsh
Keyword(s):  
T Cell Activation ◽  
Protein Tyrosine Phosphatase ◽  
Time Course ◽  
Cell Activation ◽  
Regulatory Mechanism ◽  
Transmembrane Protein ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine

We describe a potential regulatory mechanism for the transmembrane protein-tyrosine phosphatase CD45. Phosphorylation on both tyrosine and serine residues in vitro results in an activation of CD45 specifically toward one artificial substrate but not another. The activation of these kinases appears to be order dependent, as it is enhanced when phosphorylation of tyrosine precedes that of serine but phosphorylation in the reverse order yields no activation. Any of four protein-tyrosine kinases tested, in combination with the protein-serine/threonine kinase, casein kinase II, was capable of mediating this activation in vitro. The time course of phosphorylation of CD45 in response to T-cell activation is consistent with the possibility that this regulatory mechanism is utilized in vivo.

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