Retinoic acid application to chick wing buds leads to a dose-dependent reorganization of the apical ectodermal ridge that is mediated by the mesenchyme

Development ◽  
1989 ◽  
Vol 106 (4) ◽  
pp. 691-705 ◽  
Author(s):  
C. Tickle ◽  
A. Crawley ◽  
J. Farrar
Keyword(s):  
Retinoic Acid ◽  
Gap Junctions ◽  
Time Course ◽  
Apical Ectodermal Ridge ◽  
Threshold Response ◽  
Epithelial Morphology ◽  
Early Effects ◽  
High Doses ◽  
Columnar Cells ◽  
Dose Dependent

Local application of retinoic acid to wing buds of chick embryos leads to dose- and position-dependent changes in the pattern of cellular differentiation. Early effects of retinoid treatment on the apical ectodermal ridge coordinate pattern changes and morphogenesis. The length of the apical ridge increases when additional digits will form but decreases when digits are lost. These changes in length can be understood in terms of a threshold response to the local retinoid concentration that results in either disappearance or maintenance of the ridge (Lee & Tickle, J. Embryol. exp. Morph. 90, 139–169 (1985)). Here, we have analysed the mechanisms involved in ridge disappearance by locally applying retinoic acid to the apex of stage 20 chick wing buds. With this treatment regime, low doses give duplicated digit patterns and higher doses truncations. The height of the apical ridge is progressively reduced with increasing doses of retinoid and the time course of ridge flattening indicates that the height of the ridge is correlated with bud outgrowth. With high doses of retinoic acid, the typical ridge, a pseudostratified epithelium in which the columnar cells are tightly packed, disappears and the epithelium at the tip of the bud consists of loosely packed cuboidal cells. Shortly after treatment, there is a decrease in the number of gap junctions between ridge cells. This early change in cell contacts suggests that gap junctions may be involved in maintaining epithelial morphology. When treated epithelium is recombined with untreated mesenchyme, an apical ridge is reestablished and distal structures can be generated. In contrast, when treated mesenchyme is recombined with the epithelium from normal buds, only proximal structures are formed. Therefore, retinoids can lead to a reorganization of the apical ectodermal ridge which is mediated and maintained by the mesenchyme.

Intracerebroventricular injection of prostaglandin E2 increases splenic sympathetic nerve activity in rats

1995 ◽  
Vol 269 (3) ◽  
pp. R662-R668 ◽  
Author(s):  
T. Ando ◽  
T. Ichijo ◽  
T. Katafuchi ◽  
T. Hori
Keyword(s):  
Prostaglandin E2 ◽  
Sympathetic Nerve ◽  
Time Course ◽  
Sympathetic Nerve Activity ◽  
Dependent Manner ◽  
Central Administration ◽  
Nerve Activity ◽  
High Doses ◽  
Alpha Chloralose ◽  
Dose Dependent

The effects of central administration of prostaglandin E2 (PGE2) and its selective agonists on splenic sympathetic nerve activity (SNA) were investigated in urethan- and alpha-chloralose-anesthetized rats. An intra-third-cerebroventricular (13V) injection of PGE2 (0.1-10 nmol/kg) increased splenic SNA in a dose-dependent manner. An I3V injection of an EP1 agonist, 17-phenyl-omega-trinor PGE2 (1-30 nmol/kg), also resulted in a dose-dependent increase in splenic SNA, with a time course similar to that of PGE2-induced responses. In contrast, EP2 agonists, butaprost (10-100 nmol/kg I3V) and 11-deoxy-PGE1 (10-100 nmol/kg I3V), had no effect on splenic SNA. An I3V injection of M & B-28767 (an EP3/EP1 agonist, EP3 >> EP1) increased splenic SNA only at high doses (10-100 nmol/kg). Pretreatment with an EP1 antagonist, SC-19220 (200 and 500 nmol/kg), completely blocked the responses of splenic SNA to PGE2 (0.1 nmol/kg) and M & B-28767 (10 nmol/kg), respectively. These findings indicate that brain PGE2 increases splenic SNA through its action on EP1 receptors.

Retinoic acid and pattern formation in the developing chick wing: SEM and quantitative studies of early effects on the apical ectodermal ridge and bud outgrowth

Development ◽  
1985 ◽  
Vol 90 (1) ◽  
pp. 139-169
Author(s):  
J. Lee ◽  
C. Tickle
Keyword(s):  
Retinoic Acid ◽  
Local Application ◽  
Local Source ◽  
Local Concentration ◽  
Low Doses ◽  
Response Curves ◽  
Wing Patterns ◽  
Skeletal Pattern ◽  
High Doses ◽  
Dose Dependent

When retinoic acid is locally applied to the anterior margin of developing chick wing buds on ion-exchange beads, dose-dependent changes in the skeletal pattern result. At low doses, additional digits develop. At high doses, there is thinning of the symmetrical wing. Local application of retinoic acid to the apex of the bud also leads to pattern changes, but in contrast normal wing patterns are almost always obtained following application posteriorly. These effects are manifest at 6–7 days after the operation although only a brief exposure (14–20 h) to retinoic acid is required. Therefore the morphology of wing buds was studied at shorter times after the start of treatment. The local application of retinoic acid to the wing bud margin leads to changes in extent of the apical ridge that can be detected at 24 h after application. The behaviour of the apical ridge with varying doses and positions of retinoic acid application has been analysed quantitatively and dose response curves obtained. At low doses of retinoic acid, the length of the apical ridge increases or remains constant, but then progressively decreases with higher doses. The progressive obliteration of the ridge starts first near the bead and then involves more distant parts of the bud. Thus the region of the ridge affected depends on the position at which the retinoic acid is applied. We propose that these effects on the apical ridge reflect dose-dependent responses to the local concentration of retinoic acid that varies with distance from the source. At high doses, the apical ridge disappears but at low doses it is maintained. Since grafts of polarizing region tissue also have a graded effect on ridge morphology, a possible interpretation of the retinoic acid effects is that tissue adjacent to the source is converted into polarizing region tissue. Alternatively, retinoic acid may act directly on the ridge cells. The changes in the extent of the apical ridge produced by retinoic acid lead to different forms of bud outgrowth. The form of the outgrowth depends on the dose of retinoic acid, the position of application and the interaction between the effects of the local source of retinoic acid and those of the polarizing region of the host bud. These considerations give some insights into why anterior application of retinoic acid leads to the development of additional digits whereas posterior application generally gives normal wings.

Acute and early effects of aldosterone on Na-K-ATPase activity in Madin-Darby canine kidney epithelial cells

1993 ◽  
Vol 264 (6) ◽  
pp. F1021-F1026 ◽  
Author(s):  
M. Shahedi ◽  
K. Laborde ◽  
L. Bussieres ◽  
C. Sachs
Keyword(s):  
Atpase Activity ◽  
Time Course ◽  
De Novo ◽  
Mdck Cells ◽  
Early Effect ◽  
Catalytic Sites ◽  
Early Effects ◽  
Dose Dependent ◽  
De Novo Protein Synthesis ◽  
Darby Canine Kidney

The time course and mechanism of early effects of aldosterone on renal Na-K-adenosinetriphosphatase (Na-K-ATPase) activity and number of units were studied in MDCK cells. Aldosterone induced a time- and dose-dependent stimulation of Na-K-ATPase activity. The stimulatory effect of aldosterone on activity and number of pump units increased progressively and was inhibited by spironolactone. In presence of cycloheximide, the stimulatory effect of aldosterone on activity and number of catalytic sites persisted to the same extent until 30 min and decreased by 20% after 60 min. In these cells, dimethylamiloride addition during preincubation abolished the aldosterone-induced stimulation in Na-K-ATPase activity up to 60 min. In contrast, furosemide addition did not alter the effect of aldosterone on Na-K-ATPase activity. The present study demonstrates an early effect of aldosterone on Na-K-ATPase activity that can be separated into the following two successive periods: 1) increase in pump number due to insertion of presynthetized units secondary to Na entry through an amiloride-sensitive apical pathway; and 2) an increase in pump number by de novo protein synthesis.

NON-SELECTIVE INHIBITION OF BASAL GLUCAGON RELEASE BY [d-CYS14]-ANALOGUES OF SOMATOSTATIN IN THE RAT

1979 ◽  
Vol 81 (3) ◽  
pp. 315-323 ◽  
Author(s):  
FRITZ MÄRKI ◽  
BRUNO KAMBER ◽  
HANS RINK ◽  
PETER SIEBER
Keyword(s):  
Time Course ◽  
Dose Range ◽  
Subcutaneous Administration ◽  
Selective Inhibition ◽  
Glucagon Release ◽  
Basal Plasma ◽  
Dose Dependent Decrease ◽  
High Doses ◽  
Glucagon And Insulin ◽  
Dose Dependent

The effects of two [d-Cys14]-analogues of somatostatin on basal plasma levels of glucagon, insulin and glucose were determined in unanaesthetized rats to re-examine a glucagon-selective action of these peptides which has been claimed by others. Somatostatin, [d-Cys14]-somatostatin and [d-Trp8, d-Cys14]-somatostatin caused a short-lasting, dose-dependent decrease of plasma glucagon and insulin but they had no significant influence on plasma glucose. Glucagon and insulin reached the nadir 2 min after intravenous injection of the peptides (dose range 1–10 μg/kg) or 5 min after subcutaneous administration (30 and 300 μg/kg). At the nadir, insulin was decreased to a greater extent than glucagon and the effects of all three peptides were equipotent. However, in the period after the nadir and at high doses, the time-course of some effects of the analogues on either glucagon or insulin differed from that of somatostatin. Thus, these [d-Cys14]-analogues may show partial kinetic dissociation of effects on glucagon and insulin but they are not truly selective inhibitors of glucagon release.

Collagen-Induced Platelet Aggregation: -Evidence Against the Essential Role of Platelet Adenosine Diphosphate

1979 ◽  
Vol 42 (04) ◽  
pp. 1193-1206 ◽  
Author(s):  
Barbara Nunn
Keyword(s):  
Platelet Aggregation ◽  
Time Course ◽  
Essential Role ◽  
Atp Release ◽  
Adenosine Diphosphate ◽  
Human Platelets ◽  
High Doses ◽  
Induced Aggregation

SummaryThe hypothesis that platelet ADP is responsible for collagen-induced aggregation has been re-examined. It was found that the concentration of ADP obtaining in human PRP at the onset of aggregation was not sufficient to account for that aggregation. Furthermore, the time-course of collagen-induced release in human PRP was the same as that in sheep PRP where ADP does not cause release. These findings are not consistent with claims that ADP alone perpetuates a collagen-initiated release-aggregation-release sequence. The effects of high doses of collagen, which released 4-5 μM ADP, were not inhibited by 500 pM adenosine, a concentration that greatly reduced the effect of 300 μM ADP. Collagen caused aggregation in ADP-refractory PRP and in platelet suspensions unresponsive to 1 mM ADP. Thus human platelets can aggregate in response to collagen under circumstances in which they cannot respond to ADP. Apyrase inhibited aggregation and ATP release in platelet suspensions but not in human PRP. Evidence is presented that the means currently used to examine the role of ADP in aggregation require investigation.

Melatonin actions in the heart; more than a hormone

2018 ◽  
Vol 1 (1) ◽  
pp. 21-26 ◽  
Author(s):  
Darío Acuña-Castroviejo ◽  
Maria T Noguiera-Navarro ◽  
Russel J Reiter ◽  
Germaine Escames
Keyword(s):  
Cell Membranes ◽  
Myocardial Cell ◽  
Rat Tissues ◽  
Dependent Manner ◽  
Broad Distribution ◽  
Multiple Organs ◽  
High Doses ◽  
Extrapineal Melatonin ◽  
Dose Dependent ◽  
Different Doses

Due to the broad distribution of extrapineal melatonin in multiple organs and tissues, we analyzed the presence and subcellular distribution of the indoleamine in the heart of rats. Groups of sham-operated and pinealectomized rats were sacrificed at different times along the day, and the melatonin content in myocardial cell membranes, cytosol, nuclei and mitochondria, were measured. Other groups of control animals were treated with different doses of melatonin to monitor its intracellular distribution. The results show that melatonin levels in the cell membrane, cytosol, nucleus, and mitochondria vary along the day, without showing a circadian rhythm. Pinealectomized animals trend to show higher values than sham-operated rats. Exogenous administration of melatonin yields its accumulation in a dose-dependent manner in all subcellular compartments analyzed, with maximal concentrations found in cell membranes at doses of 200 mg/kg bw melatonin. Interestingly, at dose of 40 mg/kg b.w, maximal concentration of melatonin was reached in the nucleus and mitochondrion. The results confirm previous data in other rat tissues including liver and brain, and support that melatonin is not uniformly distributed in the cell, whereas high doses of melatonin may be required for therapeutic purposes.

scholarly journals Cardiac Remodeling Induced by All-Trans Retinoic Acid is Detrimental in Normal Rats

2017 ◽  
Vol 43 (4) ◽  
pp. 1449-1459 ◽  
Author(s):  
Renata A. C. Silva ◽  
Andréa F. Gonçalves ◽  
Priscila P. dos Santos ◽  
Bruna Rafacho ◽  
Renan F. T. Claro ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Retinoic Acid ◽  
Energy Metabolism ◽  
Cardiac Remodeling ◽  
Citrate Synthase ◽  
Isolated Heart ◽  
Lipid Hydroperoxide ◽  
Dependent Manner ◽  
Heart Study ◽  
Dose Dependent

Background/Aims: This study aimed to discern whether the cardiac alterations caused by retinoic acid (RA) in normal adult rats are physiologic or pathologic. Methods and Results: Wistar rats were assigned into four groups: control animals (C, n = 20) received a standard rat chow; animals fed a diet supplemented with 0.3 mg/kg/day all-trans-RA (AR1, n = 20); animals fed a diet supplemented with 5 mg/kg/day all-trans-RA (AR2, n = 20); and animals fed a diet supplemented with 10 mg/kg/day all-trans-RA (AR3, n = 20). After 2 months, the animals were submitted to echocardiogram, isolated heart study, histology, energy metabolism status, oxidative stress condition, and the signaling pathway involved in the cardiac remodeling induced by RA. RA increased myocyte cross-sectional area in a dose-dependent manner. The treatment did not change the morphological and functional variables, assessed by echocardiogram and isolated heart study. In contrast, RA changed catalases, superoxide dismutase, and glutathione peroxidases and was associated with increased values of lipid hydroperoxide, suggesting oxidative stress. RA also reduced citrate synthase, enzymatic mitochondrial complex II, ATP synthase, and enzymes of fatty acid metabolism and was associated with increased enzymes involved in glucose use. In addition, RA increased JNK 1/2 expression, without changes in TGF-β, PI3K, AKT, NFκB, S6K, and ERK. Conclusion: In normal rats, RA induces cardiac hypertrophy in a dose-dependent manner. The non-participation of the PI3K/Akt pathway, associated with the participation of the JNK pathway, oxidative stress, and changes in energy metabolism, suggests that cardiac remodeling induced by RA supplementation is deleterious.

EFFECT OF INTRAVENTRICULAR ADMINISTRATION OF NORADRENALINE ON WATER DIURESIS IN GOATS

1975 ◽  
Vol 66 (3) ◽  
pp. 375-383 ◽  
Author(s):  
G. VANDEPUTTE-VAN MESSOM ◽  
G. PEETERS
Keyword(s):  
Intraventricular Administration ◽  
Excretion Ratio ◽  
Dose Response Relationship ◽  
Water Diuresis ◽  
3Rd Ventricle ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
High Doses ◽  
Excretion Rates ◽  
Dose Dependent

SUMMARY During water diuresis in conscious goats, noradrenaline (NA), its antagonists phentolamine, phenoxybenzamine and propranolol and also atropine were administered into the 3rd ventricle. The subsequent effects on water diuresis and on the excretion rates of Na+, K+ and Cl− were investigated. Infusion of NA into the 3rd ventricle induced a strong and significant antidiuretic response and a decrease in the Na+: K+ excretion ratio; these effects were dose-dependent. High doses of NA produced a significant increase in urinary K+ excretion. Similar results were observed after i.v. administration of arginine-vasopressin. Pretreatment with phentolamine injected into the 3rd ventricle produced a dose-dependent inhibition of the NA-induced antidiuretic effects. Phenoxybenzamine also blocked the response to NA but a dose-response relationship was not apparent. Atropine and propranolol did not block the response to NA.

scholarly journals Complexing of the CD-3 subunit by a monoclonal antibody activates a microtubule-associated protein 2 (MAP-2) serine kinase in Jurkat cells

1989 ◽  
Vol 262 (2) ◽  
pp. 449-456 ◽  
Author(s):  
C Hanekom ◽  
A Nel ◽  
C Gittinger ◽  
A Rheeder ◽  
G Landreth
Keyword(s):  
T Cells ◽  
Time Course ◽  
Gel Filtration ◽  
Maximal Activity ◽  
Jurkat Cells ◽  
Serine Kinase ◽  
Transient Activation ◽  
Normal Human ◽  
Dose Dependent

Treatment of Jurkat T-cells with anti-CD-3 monoclonal antibodies resulted in the rapid and transient activation of a serine kinase which utilized the microtubule-associated protein, MAP-2, as a substrate in vitro. The kinase was also activated on treatment of Jurkat cells with phytohaemagglutinin, but with a different time course. The activation of the MAP-2 kinase by anti-CD-3 antibodies was dose-dependent, with maximal activity observed at concentrations of greater than 500 ng/ml. Normal human E-rosette-positive T-cells also exhibited induction of MAP-2 kinase activity during anti-CD-3 treatment. The enzyme was optimally active in the presence of 2 mM-Mn2+; lower levels of activity were observed with Mg2+, even at concentrations up to 20 mM. The kinase was partially purified by passage over DE-52 Sephacel with the activity eluting as a single peak at 0.25 M-NaCl. The molecular mass was estimated to be 45 kDa by gel filtration. The activation of the MAP-2 kinase was probably due to phosphorylation of this enzyme as treatment with alkaline phosphatase diminished its activity. These data demonstrate that the stimulation of T-cells through the CD-3 complex results in the activation of a novel serine kinase which may be critically involved in signal transduction in these cells.

Ultrastructural analysis of the apical ectodermal ridge during vertebrate limb morphogenesis

Development ◽  
1977 ◽  
Vol 41 (1) ◽  
pp. 223-232
Author(s):  
John F. Fallon ◽  
Robert O. Kelley
Keyword(s):  
Electron Microscopy ◽  
Gap Junctions ◽  
Freeze Fracture ◽  
Apical Ectodermal Ridge ◽  
Structural Requirements ◽  
Limb Morphogenesis ◽  
Vertebrate Limb ◽  
The Difference ◽  
Freeze Fracture Electron Microscopy ◽  
Fracture Electron

The fine structure of the apical ectodermal ridge of five phylogenetically divergent orders of mammals and two orders of birds was examined using transmission and freeze fracture electron microscopy. Numerous large gap junctions were found in all apical ectodermal ridges studied. This was in contrast to the dorsal and ventral limb ectoderms where gap junctions were always very small and sparsely distributed. Thus, gap junctions distinguish the inductively active apical epithelium from the adjacent dorsal and ventral ectoderms. The distribution of gap junctions in the ridge was different between birds and mammals but characteristic within the two classes. Birds, with a pseudostratified columnar apical ridge, had the heaviest concentration of gap junctions at the base of each ridge cell close to the point where contact was made with the basal lamina. Whereas mammals, with a stratified cuboidal to squamous apical ridge, had a more uniform distribution of gap junctions throughout the apical epithelium. The difference in distribution for each class may reflect structural requirements for coupling of cells in the entire ridge. We propose that all cells of the apical ridges of birds and mammals are electrotonically and/or metabolically coupled and that this may be a requirement for the integrated function of the ridge during limb morphogenesis.

Sign in / Sign up

Export Citation Format

Share Document