Endogenous ACh tonically stimulates ANP secretion in rat atria

2013 ◽  
Vol 305 (7) ◽  
pp. H1050-H1056 ◽  
Author(s):  
Hye Yoom Kim ◽  
Kyung Woo Cho ◽  
Dong Yuan Xu ◽  
Dae Gill Kang ◽  
Ho Sub Lee
Keyword(s):  
Acetylcholinesterase Inhibition ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Rat Atria ◽  
Rate Limiting Step ◽  
Induced Changes ◽  
Rate Limiting ◽  
Muscarinic Ach Receptor ◽  
High Affinity Choline Transporter

Exogenous acetylcholine (ACh) is known to stimulate atrial natriuretic peptide (ANP) secretion concomitantly with a decrease in atrial pulse pressure. However, the role of intrinsic ACh in the regulation of ANP secretion remains unknown. Recently, it was shown that nonneuronal and neuronal ACh is present in the cardiac atria. From this finding we hypothesize that endogenously released ACh is involved in the regulation of ANP secretion in an autocrine or paracrine manner in the atria. Experiments were performed in isolated beating rat atria. ANP was measured using radioimmunoassay. To increase the availability of the ACh in the extracellular space of the atrium, its degradation was inhibited with an inhibitor of acetylcholinesterase. Acetylcholinesterase inhibition with physostigmine increased ANP secretion concomitantly with a decrease in atrial dynamics in a concentration-dependent manner. Inhibitors of M2 muscarinic ACh receptor (mAChR), methoctramine, and ACh-activated K+ (KACh+) channels, tertiapin-Q, abolished the physostigmine-induced changes. The effects were not observed in the atria from rats treated with pertussis toxin. Furthermore, the physostigmine-induced effects were attenuated by an inhibitor of high-affinity choline transporter, hemicholinium-3, which is a rate-limiting step of ACh synthesis. Inhibitors of the mAChR signaling pathway and ACh synthesis also attenuated the basal levels of ANP secretion and accentuated atrial dynamics. These findings suggest that endogenously released ACh tonically stimulates ANP secretion from atrial cardiomyocytes via activation of M2 mAChR-Gi/o-KACh+ channel signaling. It is also suggested that the ACh-ANP signaling is implicated in cardiac physiology and pathophysiology.

Histamine inhibits atrial myocytic ANP release via H2 receptor-cAMP-protein kinase signaling

2003 ◽  
Vol 285 (2) ◽  
pp. R380-R393 ◽  
Author(s):  
Dan Li ◽  
Jin Fu Wen ◽  
Jing Yu Jin ◽  
Hua Jin ◽  
Hai Sun Ann ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Selective Inhibitor ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Camp Analog ◽  
Induced Changes ◽  
Protein Kinase Signaling ◽  
Dose Dependent ◽  
Rabbit Atria

Changes in cyclic nucleotide production and atrial dynamics have been known to modulate atrial natriuretic peptide (ANP) release. Although cardiac atrium expresses histamine receptors and contains histamine, the role of histamine in the regulation of ANP release has to be defined. The purpose of the present study was to define the effect of histamine on the regulation of ANP release in perfused beating rabbit atria. Histamine decreased ANP release concomitantly with increases in cAMP efflux and atrial dynamics in a concentration-dependent manner. Histamine-induced decrease in ANP release was a function of an increase in cAMP production. Blockade of histamine H2 receptor with cimetidine but not of H1 receptor with triprolidine abolished the responses of histamine. Cell-permeable cAMP analog, 8-Br-cAMP, mimicked the effects of histamine, and the responses were dose-dependent and blocked by a protein kinase A (PKA)-selective inhibitor, KT5720. Nifedipine failed to modulate histamine-induced decrease in ANP release. Protein kinase nonselective inhibitor staurosporine blocked histamine-induced changes in a concentration-dependent manner. KT5720 and RP-adenosine 3′,5′-cyclic monophosphorothioate, another PKA-selective inhibitor, attenuated histamine-induced changes. These results suggest that histamine decreases atrial ANP release by H2 receptor-cAMP signaling via PKA-dependent and -independent pathways.

scholarly journals Block of current through single calcium channels by Fe, Co, and Ni. Location of the transition metal binding site in the pore.

1991 ◽  
Vol 97 (2) ◽  
pp. 351-367 ◽  
Author(s):  
B D Winegar ◽  
R Kelly ◽  
J B Lansman
Keyword(s):  
Metal Binding ◽  
The Other ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Coulombic Interactions ◽  
Rate Limiting Step ◽  
Ion Size ◽  
Rate Limiting ◽  
Kinetics Of ◽  
Ca2 Channels

The blocking actions of Fe2+, Co2+, and Ni2+ on unitary currents carried by Ba2+ through single dihydropyridine-sensitive Ca2+ channels were recorded from cell-attached patches on myotubes from the mouse C2 cell line. Adding millimolar concentrations of blocker to patch electrodes containing 110 mM BaCl2 produced discrete excursions to the closed channel level. The kinetics of blocking and unblocking were well described with a simple model of open channel block. Hyperpolarization speeded the exit of all of the blockers from the channel, as expected if the blocking site resides within the pore. The block by Ni2+ differs from that produced by Fe2+ and Co2+ because Ni2+ enters the channel approximately 20 times more slowly and exits approximately 50 times more slowly. Ni2+ also differs from the other transition metals because at millimolar concentrations it reduces the amplitude of the unitary current in a concentration-dependent manner. The results are consistent with the idea that the rate-limiting step for ion entry into the channel is water loss at its inner coordination sphere; unblocking, on the other hand, cannot be explained in terms of simple coulombic interactions arising from differences in ion size.

Hydrogen Diffusion and Thermal Equilibrium of Electronic States in a-Si:H

1987 ◽  
Vol 95 ◽  
Author(s):  
R. A. Street
Keyword(s):  
Thermal Equilibrium ◽  
Hydrogen Diffusion ◽  
Electronic States ◽  
Thermally Induced ◽  
Rate Limiting Step ◽  
Induced Changes ◽  
Rate Limiting ◽  
Hydrogenated Amorphous ◽  
Diffusion Of Hydrogen

AbstractThis paper reviews the recent evidence for thermal equilibrium effects in the electronic behavior of hydrogenated amorphous silicon, and relates the thermally induced changes to the motion of bonded hydrogen. The electronic properties are studied through measurements of d.c conductivity and-.weep out, and the role of hydrogen is explored through its diffusion. The magnitude and doping dependence of the diffusion coefficient DH matches the data on the equilibration of the electronic states. Furthermore both the diffusibn and the relaxation can be described by the same dispersive time dependence. It is argued that the diffusion of hydrogen is the rate limiting step in the the equilibration mechanisms and determines the kinetics.

Effects of inhibitors of arachidonic acid turnover on the production of prostaglandins by the guinea-pig uterus

Reproduction ◽  
2000 ◽  
pp. 181-186 ◽  
Author(s):  
SJ Norman ◽  
NL Poyser
Keyword(s):  
Arachidonic Acid ◽  
Guinea Pig ◽  
Aristolochic Acid ◽  
Acid Uptake ◽  
Dependent Manner ◽  
Inhibitory Effects ◽  
Concentration Dependent Manner ◽  
Rate Limiting Step ◽  
Free Arachidonic Acid ◽  
Rate Limiting

The supply of free arachidonic acid from phospholipids is generally regarded as the rate-limiting step for prostaglandin (PG) synthesis by tissues. Two enzymes involved in arachidonic acid uptake into, and release from, phospholipids are acyl-CoA:lysophospholipid acyltransferase (ACLAT) and phospholipase A2 (PLA2), respectively. PGF2 alpha produced by the endometrium induces luteolysis in several species including guinea-pigs. Thimerosal, an inhibitor of ACLAT, and aristolochic acid, an inhibitor of PLA2, both reduced, in a concentration-dependent manner, the output of PGF2 alpha from guinea-pig endometrium cultured for 24 h on days 7 and 15 of the oestrous cycle. This study showed that the continual production of PGF 2 alpha by guinea-pig endometrium is not only dependent upon the activity of PLA2 for releasing free arachidonic acid for PGF2 alpha synthesis, but also on the incorporation of arachidonic acid into the phospholipid pool by the activity of ACLAT. The inhibitory effects of thimerosal and aristolochic acid on the outputs of PGE2 and 6-keto-PGF1 alpha were less marked, particularly on day 7 when the low output of PGE2 was unaffected and the output of 6-keto-PGF1 alpha was increased at the lower concentrations of thimerosal. This finding indicates that there are different pools of arachidonic acid bound as phospholipid for the syntheses of PGF2 alpha and 6-keto-PGF1 alpha by guinea-pig endometrium.

scholarly journals Choline acetyltransferase–expressing T cells are required to control chronic viral infection

Science ◽  
2019 ◽  
Vol 363 (6427) ◽  
pp. 639-644 ◽  
Author(s):  
Maureen A. Cox ◽  
Gordon S. Duncan ◽  
Gloria H. Y. Lin ◽  
Benjamin E. Steinberg ◽  
Lisa X. Yu ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Viral Infection ◽  
Choline Acetyltransferase ◽  
Lymphocytic Choriomeningitis ◽  
Dependent Manner ◽  
T Cell Migration ◽  
Rate Limiting Step ◽  
Rate Limiting

Although widely studied as a neurotransmitter, T cell–derived acetylcholine (ACh) has recently been reported to play an important role in regulating immunity. However, the role of lymphocyte-derived ACh in viral infection is unknown. Here, we show that the enzyme choline acetyltransferase (ChAT), which catalyzes the rate-limiting step of ACh production, is robustly induced in both CD4+ and CD8+ T cells during lymphocytic choriomeningitis virus (LCMV) infection in an IL-21–dependent manner. Deletion of Chat within the T cell compartment in mice ablated vasodilation in response to infection, impaired the migration of antiviral T cells into infected tissues, and ultimately compromised the control of chronic LCMV clone 13 infection. Our results reveal a genetic proof of function for ChAT in T cells during viral infection and identify a pathway of T cell migration that sustains antiviral immunity.

The P-element-induced silencing effect of KP transposons is dose dependent in Drosophila melanogaster

Genome ◽  
2011 ◽  
Vol 54 (9) ◽  
pp. 752-762 ◽  
Author(s):  
Alireza Sameny ◽  
John Locke
Keyword(s):  
Drosophila Melanogaster ◽  
Critical Role ◽  
Mutagenic Effect ◽  
P Element ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
P Elements ◽  
Single Well ◽  
Dose Dependent

Transposable elements are found in the genomes of all eukaryotes and play a critical role in altering gene expression and genome organization. In Drosophila melanogaster, transposable P elements are responsible for the phenomenon of hybrid dysgenesis. KP elements, a deletion-derivative of the complete P element, can suppress this mutagenic effect. KP elements can also silence the expression of certain other P-element-mediated transgenes in a process called P-element-dependent silencing (PDS), which is thought to involve the recruitment of heterochromatin proteins. To explore the mechanism of this silencing, we have mobilized KP elements to create a series of strains that contain single, well-defined KP insertions that show PDS. To understand the quantitative role of KP elements in PDS, these single inserts were combined in a series of crosses to obtain genotypes with zero, one, or two KP elements, from which we could examine the effect of KP gene dose. The extent of PDS in these genotypes was shown to be dose dependent in a logarithmic rather than linear fashion. A logarithmic dose dependency is consistent with the KP products interacting with heterochromatic proteins in a concentration-dependent manner such that two molecules are needed to induce gene silencing.

Protein kinase C potentiates cAMP-stimulated mouse duodenal mucosal bicarbonate secretion in vitro

2004 ◽  
Vol 286 (5) ◽  
pp. G814-G821 ◽  
Author(s):  
Bi-Guang Tuo ◽  
Jimmy Y. C. Chow ◽  
Kim E. Barrett ◽  
Jon I. Isenberg
Keyword(s):  
Short Circuit ◽  
Short Circuit Current ◽  
Duodenal Mucosa ◽  
Bicarbonate Secretion ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Ussing Chambers ◽  
Duodenal Bicarbonate Secretion

PKC has been shown to regulate epithelial Cl- secretion in a variety of models. However, the role of PKC in duodenal mucosal bicarbonate secretion is less clear. We aimed to investigate the role of PKC in regulation of duodenal mucosal bicarbonate secretion. Bicarbonate secretion by murine duodenal mucosa was examined in vitro in Ussing chambers using a pH-stat technique. PKC isoform expression and activity were assessed by Western blotting and in vitro kinase assays, respectively. PMA (an activator of PKC) alone had no effect on duodenal bicarbonate secretion or short-circuit current ( Isc). When PMA and dibutyryl-cAMP (db-cAMP) were added simultaneously, PMA failed to alter db-cAMP-stimulated duodenal bicarbonate secretion or Isc ( P > 0.05). However, a 1-h preincubation with PMA potentiated db-cAMP-stimulated duodenal bicarbonate secretion and Isc in a concentration-dependent manner (from 10-8 to 10-5M) ( P < 0.05). PMA preincubation had no effects on carbachol- or heat-stable toxin-stimulated bicarbonate secretion. Western blot analysis revealed that PKCα, -γ, -ϵ, -θ, -μ, and -ι/λ were expressed in murine duodenal mucosa. Ro 31–8220 (an inhibitor active against PKCϵ, -α, -β, and -γ), but not Gö 6983 (an inhibitor active against PKCα, -γ, -β, and -δ), reversed the potentiating effect of PMA on db-cAMP-stimulated bicarbonate secretion. PMA also time- and concentration-dependently increased the activity of PKCϵ, an effect that was prevented by Ro 31–8220 but not Gö 6983. These results demonstrate that activation of PKC potentiates cAMP-stimulated duodenal bicarbonate secretion, whereas it does not modify basal secretion. The effect of PKC on cAMP-stimulated bicarbonate secretion is mediated by the PKCϵ isoform.

scholarly journals Sec1p directly stimulates SNARE-mediated membrane fusion in vitro

2004 ◽  
Vol 167 (1) ◽  
pp. 75-85 ◽  
Author(s):  
Brenton L. Scott ◽  
Jeffrey S. Van Komen ◽  
Hassan Irshad ◽  
Song Liu ◽  
Kirilee A. Wilson ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Membrane Fusion ◽  
Membrane Trafficking ◽  
Snare Complex ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Bud Neck ◽  
Precise Role

Sec1 proteins are critical players in membrane trafficking, yet their precise role remains unknown. We have examined the role of Sec1p in the regulation of post-Golgi secretion in Saccharomyces cerevisiae. Indirect immunofluorescence shows that endogenous Sec1p is found primarily at the bud neck in newly budded cells and in patches broadly distributed within the plasma membrane in unbudded cells. Recombinant Sec1p binds strongly to the t-SNARE complex (Sso1p/Sec9c) as well as to the fully assembled ternary SNARE complex (Sso1p/Sec9c;Snc2p), but also binds weakly to free Sso1p. We used recombinant Sec1p to test Sec1p function using a well-characterized SNARE-mediated membrane fusion assay. The addition of Sec1p to a traditional in vitro fusion assay moderately stimulates fusion; however, when Sec1p is allowed to bind to SNAREs before reconstitution, significantly more Sec1p binding is detected and fusion is stimulated in a concentration-dependent manner. These data strongly argue that Sec1p directly stimulates SNARE-mediated membrane fusion.

scholarly journals Folding initiation sites and protein folding.

1999 ◽  
Vol 46 (3) ◽  
pp. 487-508 ◽  
Author(s):  
M Dadlez
Keyword(s):  
Protein Folding ◽  
Protein Fragments ◽  
Denatured State ◽  
Local Structures ◽  
Rate Limiting Step ◽  
Structural Preferences ◽  
Low Levels ◽  
Rate Limiting ◽  
Transition State Barrier

The paper discusses the role of local structural preferences of protein segments in the folding of proteins. First a short overview of the local, secondary structures detected in peptides, protein fragments, denatured proteins and early folding intermediates is given. Next the discussion of their role in protein folding is presented based on recent literature and data obtained in our laboratory. In conclusion it is pointed out that, during folding, local structures populated at low levels in denatured state may facilitate the crossing of the folding transition state barrier, and consequently accelerate the rate limiting step in folding. However, the data show that this effect does not follow simple rules.

scholarly journals Lead induced changes in biomarkers and proteome map of Chicory (Cichorium intybus L.)

2020 ◽  
pp. 111-116
Author(s):  
Bisma Malik ◽  
Tanveer Bilal Pirzadah
Keyword(s):  
Contaminated Soils ◽  
Research Work ◽  
Biomass Accumulation ◽  
Cichorium Intybus ◽  
Dependent Manner ◽  
Proteomics Data ◽  
Concentration Dependent Manner ◽  
Pb Stress ◽  
Metal Treatment ◽  
Induced Changes

Lead (Pb) toxicity is a serious environmental problem as it affects the food production by interfering plant growth and development, thus declines the production yield. In the present research work, Cichorium intybus L. plants were subjected to different concentrations of Pb (0, 100, 200 and 300µM) upto 46days to determine the oxidative stress. The length of root and shoot, accumulation of biomass were estimated along with the changes in biomarkers (H2O2 and TBARS). Further proteomic analysis of chicory leaves (46days old) at 300µM Pb concentration was done to identify the proteins of interest. The root growth increased significantly in a concentration-dependent manner however; shoot growth, biomass accumulation declined significantly with Pb stress compared to control. Changes in biomarkers (H2O2 and TBARS) content elevated with the increment in the concentration of metal treatment but exhibited a gradual decline at 300µM Pb treatment.. Proteomics data of 46days old chicory plants under 300 µM Pb stress analyzed by PDQuest software detected approximately 168 protein spots on each gel and 81 spots were differentially expressed in which 16 were up-regulated and 13 were down-regulated. The present study suggested that chicory possess a strong antioxidative defense system to combat Pb stress and thus could be explored for cultivation in Pb contaminated soils.

Sign in / Sign up

Export Citation Format

Share Document