Bursting properties of caudal neurosecretory cells in the flounder Platichthys flesus, in vitro

2001 ◽  
Vol 204 (15) ◽  
pp. 2733-2739 ◽  
Author(s):  
M. J. Brierley ◽  
A. J. Ashworth ◽  
J. R. Banks ◽  
R. J. Balment ◽  
C. R. McCrohan

SUMMARY Bursting activity in type 1 Dahlgren cells was studied using intra- and extracellular recording from an in vitro preparation of the caudal neurosecretory system of the euryhaline flounder. 45% of cells showed spontaneous bursts of approximately 120s duration and 380s cycle period. Similar bursts were triggered by short duration (<5s) depolarising or hyperpolarising pulses. Cells displayed a characteristic depolarising after potential, following either an action potential with associated afterhyperpolarisation, or a hyperpolarising current pulse. This depolarising after potential was related to a ‘sag’ potential, which developed during the hyperpolarising pulse. Both the depolarising after potential and the sag potential occurred only in cells at more depolarised (<60mV) holding potentials. In addition, the amplitude of the depolarising after potential was dependent on the amplitude and the duration of the hyperpolarising pulse. The depolarising after potential following action potentials may provide a mechanism for facilitating repetitive firing during a burst. Extracellular recording revealed similar bursting in individual units which was not, however, synchronised between units. Spontaneous bursting activity recorded both intra- and extracellularly was inhibited by application of a known neuromodulator of the system, 5-hydroxytryptamine. This study provides a basis for investigating the relationship between physiological status, Dahlgren cell activity and neuropeptide secretion.

Parasitology ◽  
1981 ◽  
Vol 83 (2) ◽  
pp. 243-247 ◽  
Author(s):  
Margaretha K. S. Gustafsson ◽  
Marianne C. Wikgren

SUMMARYThe activation of the peptidergic neurosecretory system in Diphyllobothrium dendriticum was studied following cultivation of plerocercoids for short times in vitro and in vivo. In the plerocercoid the neurosecretory cells gave a very weak reaction with paraldehyde fuchsin (PAF). After cultivation for 1 h large numbers of neurosecretory cells filled with PAF-positive granules were evident. The significance of the activation of the neurosecretory system during the transfer of the worm from the cold-blooded fish host to the warm-blooded final host is discussed.


1972 ◽  
Vol 52 (3) ◽  
pp. 567-574 ◽  
Author(s):  
A. BERLIND

SUMMARY Extracts of the urophysis of the teleost Gillichthys mirabilis and material released from intact cells induced contraction of the Gillichthys sperm duct in vitro. Acetylcholine and 5-hydroxytryptamine also caused sperm-duct contraction, but specific blocking substances left the response to urophysial material unaltered. Adrenaline and noradrenaline inhibited the response of the sperm duct to urophysis extracts. The active factor was destroyed by trypsin, and had similar chromatographic properties to the peptidic teleost bladder-contracting factor also found in the urophysis. A role of this agent in spawning or other aspects of reproduction is suggested.


1983 ◽  
Vol 61 (12) ◽  
pp. 2856-2867 ◽  
Author(s):  
Laurent Gauthier ◽  
Céline Audet ◽  
Gaston Chevalier

The innervation of the caudal neurosecretory system of the brook trout, Salvelinus fontinalis, was studied under light and electron microscopy in order to characterize its nature, distribution, and regulatory function over the activity of the caudal neurosecretory cells. A dual innervation of the cell bodies and axons of neurosecretory cells was disclosed. One type of axosomatic connection exhibited small lucent vesicles and large dense-cored granules. These boutons were identified as monoaminergic since they appeared depleted after reserpine treatment and they were selectively labeled with 5-OH-dopamine. In fish exposed to demineralized water, reserpine induced a condition that stimulated the synthetic activity of caudal neurosecretory cells, a clear reduction of this activity, according to morphometric (cell and nucleus diameters) and ultrastructural criteria (dimensions of the Golgi complex). By comparison, no significant variation of the synthetic activity was noted in freshwater-adapted trout treated with reserpine. A second type of innervation was also identified as cholinergic by histochemical localization of acetylcholinesterase. Electron microscopic analysis also revealed axosomatic and axoaxonic cholinergic synaptic connections with characteristic small 500-Å diameter lucent vesicles. The injection of fenitrothion, an anticholinesterase agent, enhanced discharge of neurosecretory material from axonal endings of caudal cells while the synthetic activity did not appear to be modified. Our findings suggest an important role of aminergic and cholinergic controls over the response of the caudal neurosecretory system of Salvelinus fontinalis during hyperosmotic adaptation.


2018 ◽  
Vol 29 ◽  
pp. viii103
Author(s):  
J. Zimmermann ◽  
T. Remus ◽  
G. Lemercier ◽  
D. Barker ◽  
D. Obrecht ◽  
...  

2021 ◽  
Vol 19 ◽  
pp. 228080002110068
Author(s):  
Hsien-Te Chen ◽  
Hsin-I Lin ◽  
Chi-Jen Chung ◽  
Chih-Hsin Tang ◽  
Ju-Liang He

Here, we present a bone implant system of phase-oriented titanium dioxide (TiO2) fabricated by the micro-arc oxidation method (MAO) on β-Ti to facilitate improved osseointegration. This (101) rutile-phase-dominant MAO TiO2 (R-TiO2) is biocompatible due to its high surface roughness, bone-mimetic structure, and preferential crystalline orientation. Furthermore, (101) R-TiO2 possesses active and abundant hydroxyl groups that play a significant role in enhancing hydroxyapatite formation and cell adhesion and promote cell activity leading to osseointegration. The implants had been elicited their favorable cellular behavior in vitro in the previous publications; in addition, they exhibit excellent shear strength and promote bone–implant contact, osteogenesis, and tissue formation in vivo. Hence, it can be concluded that this MAO R-TiO2 bone implant system provides a favorable active surface for efficient osseointegration and is suitable for clinical applications.


2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A198-A198
Author(s):  
Tingting Zhong ◽  
Xinghua Pang ◽  
Zhaoliang Huang ◽  
Na Chen ◽  
Xiaoping Jin ◽  
...  

BackgroundTIGIT is an inhibitory receptor mainly expressed on natural killer (NK) cells, CD8+ T cells, CD4+ T cells and Treg cells. TIGIT competes with CD226 for binding with CD155. In cancers, CD155 has been reported to up-regulate on tumor cells, and TIGIT was found to increase on TILs.1 Activation of TIGIT/CD155 pathway would mediate immunosuppression in tumor; while blockade of TIGIT promotes anti-tumor immune response.MethodsAK126 and AK113 are two humanized anti-human TIGIT monoclonal antibodies developed by Akesobio. Binding activity of AK126 and AK113 to human TIGIT, and competitive binding activity with CD155 and CD112, were performed by using ELISA, Fortebio, and FACS assays. Cross-reactivity with cynomolgus monkey TIGIT and epitope binning were also tested by ELISA assay. In-vitro assay to investigate the activity to promote IL-2 secretion was performed in mixed-culture of Jurkat-TIGIT cells and THP-1 cells.ResultsAK126 and AK113 could specifically bind to human TIGIT with comparative affinity and effectively blocked the binding of human CD155 and CD112 to human TIGIT. X-ray crystal structure of TIGIT and PVR revealed the C’-C’’ loop and FG loop regions of TIGIT are the main PVR interaction regions.2 The only amino acid residue differences in these regions between human and monkey TIGIT are 70C and 73D. AK126 binds to both human and monkey TIGIT, AK113 binds only to monkey TIGIT. This suggests that these residues are required for AK113 binding to human TIGIT, but not required for AK126. Interestingly, results from cell-based assays indicated that AK126 and AK113 showed significantly different activity to induce IL-2 secretion in mixed-culture of Jurkat-TIGIT cells and THP-1 cells (figure 1A and B), in which AK126 had a comparable capacity of activity to 22G2, a leading TIGIT mAb developed by another company, to induce IL-2 secretion, while, AK113 showed a significantly higher capacity than 22G2 and AK126.Abstract 184 Figure 1Anti-TIGIT Antibodies Rescues IL-2 Production in Vitro T-Cell Activity Assay in a dose dependent manner. Jurkat-TIGIT cells (Jurkat cells engineered to over-express human TIGIT) were co-cultured with THP-1 cells, and stimulated with plate-bound anti-CD3 mAb in the presence of TIGIT ligand CD155 (A) or CD112 (B) with anti-TIGIT antibodies. After incubated for 48h at 37° C and 5.0% CO2, IL-2 levels were assessed in culture supernatants by ELISA. Data shown as mean with SEM for n = 2.ConclusionsWe discovered two distinct types of TIGIT antibodies with differences in both epitope binding and functional activity. The mechanism of action and clinical significance of these antibodies require further investigation.ReferencesSolomon BL, Garrido-Laguna I. TIGIT: a novel immunotherapy target moving from bench to bedside. Cancer Immunol Immunother 2018;67:1659–1667.Stengel KF, Harden-Bowles K, Yu X, et al. Structure of TIGIT immunoreceptor bound to poliovirus receptor reveals a cell-cell adhesion and signaling mechanism that requires cis-trans receptor clustering. Proc Natl Acad Sci USA 2012;109:5399–5404.


2003 ◽  
Vol 90 (3) ◽  
pp. 1635-1642 ◽  
Author(s):  
Ilya A. Rybak ◽  
Krzysztof Ptak ◽  
Natalia A. Shevtsova ◽  
Donald R. McCrimmon

Rapidly inactivating and persistent sodium currents have been characterized in acutely dissociated neurons from the area of rostroventrolateral medulla that included the pre-Bötzinger Complex. As demonstrated in many studies in vitro, this area can generate endogenous rhythmic bursting activity. Experiments were performed on neonate and young rats (P1-15). Neurons were investigated using the whole cell voltage-clamp technique. Standard activation and inactivation protocols were used to characterize the steady-state and kinetic properties of the rapidly inactivating sodium current. Slow depolarizing ramp protocols were used to characterize the noninactivating sodium current. The “window” component of the rapidly inactivating sodium current was calculated using mathematical modeling. The persistent sodium current was revealed by subtraction of the window current from the total noninactivating sodium current. Our results provide evidence of the presence of persistent sodium currents in neurons of the rat rostroventrolateral medulla and determine voltage-gated characteristics of activation and inactivation of rapidly inactivating and persistent sodium channels in these neurons.


2016 ◽  
Vol 60 (8) ◽  
pp. 4830-4839 ◽  
Author(s):  
Christopher M. Tan ◽  
Charles J. Gill ◽  
Jin Wu ◽  
Nathalie Toussaint ◽  
Jingjun Yin ◽  
...  

ABSTRACTOxabicyclooctane-linked novel bacterial topoisomerase inhibitors (NBTIs) represent a new class of recently described antibacterial agents with broad-spectrum activity. NBTIs dually inhibit the clinically validated bacterial targets DNA gyrase and topoisomerase IV and have been shown to bind distinctly from known classes of antibacterial agents directed against these targets. Herein we report the molecular, cellular, andin vivocharacterization of AM-8722 as a representative N-alkylated-1,5-naphthyridone left-hand-side-substituted NBTI. Consistent with its mode of action, macromolecular labeling studies revealed a specific effect of AM-8722 to dose dependently inhibit bacterial DNA synthesis. AM-8722 displayed greater intrinsic enzymatic potency than levofloxacin versus both DNA gyrase and topoisomerase IV fromStaphylococcus aureusandEscherichia coliand displayed selectivity against human topoisomerase II. AM-8722 was rapidly bactericidal and exhibited whole-cell activity versus a range of Gram-negative and Gram-positive organisms, with no whole-cell potency shift due to the presence of DNA or human serum. Frequency-of-resistance studies demonstrated an acceptable rate of resistance emergencein vitroat concentrations 16- to 32-fold the MIC. AM-8722 displayed acceptable pharmacokinetic properties and was shown to be efficacious in mouse models of bacterial septicemia. Overall, AM-8722 is a selective and potent NBTI that displays broad-spectrum antimicrobial activityin vitroandin vivo.


Sign in / Sign up

Export Citation Format

Share Document