scholarly journals Selective inhibition of Zn2+-glycerophosphocholine cholinephosphodiesterase by tellurium tetrachloride

1992 ◽  
Vol 284 (3) ◽  
pp. 641-643 ◽  
Author(s):  
D E Sok ◽  
M R Kim
Keyword(s):  
Metal Ions ◽  
Mouse Brain ◽  
Selective Inhibition ◽  
Inhibitory Effect ◽  
Physiological Conditions ◽  
Neutral Ph ◽  
Tellurium Tetrachloride ◽  
Hydrolysis Of ◽  
Competitive Pattern

A Zn(2+)-glycerophosphocholine cholinephosphodiesterase (EC 3.1.4.38) purified from mouse brain was found to be reversibly inhibited by tellurium tetrachloride. This effect was characterized by a competitive pattern of inhibition, with apparent Ki values of 0.7 microM and 1.5 microM for the hydrolysis of p-nitrophenylphosphocholine and glycerophosphocholine respectively. Interestingly, the inhibitory effect of tellurium tetrachloride was found to be greatly potentiated by tetramethylammonium salt, indicative of a synergistic interaction between the two compounds. Additionally, it was observed that the effect of tellurium tetrachloride was not affected by a number of other metal ions, and was more pronounced at neutral pH, suggesting that the inhibitory role of the tellurium tetrachloride may be of importance under physiological conditions. Thus Zn(2+)-glycerophosphocholine cholinephosphodiesterase is proposed to be one of the target enzymes which is susceptible to the inhibitory effect of tellurium tetrachloride.

scholarly journals Rostral ventral medulla 5-HT1A receptors selectively inhibit the somatosympathetic reflex

2001 ◽  
Vol 280 (5) ◽  
pp. R1261-R1268 ◽  
Author(s):  
Takashi Miyawaki ◽  
Ann K. Goodchild ◽  
Paul M. Pilowsky
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Sympathetic Nerve Activity ◽  
Selective Inhibition ◽  
Inhibitory Effect ◽  
Ventrolateral Medulla ◽  
Arterial Blood ◽  
Potent Inhibition ◽  
Somatosympathetic Reflex

The role of the 5-hydroxytryptamine (5-HT1A) receptors in the rostral ventrolateral medulla (RVLM) on somatosympathetic, baroreceptor, and chemoreceptor reflexes was examined in anesthetized rats. Microinjection of the selective 5-HT1A agonist 8-hydroxy-di- n-propylamino tetralin (8-OH-DPAT) decreased arterial blood pressure and splanchnic sympathetic nerve activity (SNA). Electrical stimulation of the hindlimb evoked early and late excitatory sympathetic responses. Bilateral microinjection in the RVLM of 8-OH-DPAT markedly attenuated both the early and late responses. This potent inhibition of the somatosympathetic reflex persisted even after SNA and arterial blood pressure returned to preinjection levels. Preinjection of the selective 5-HT1A antagonist NAN-190 in the RVLM blocked the sympathoinhibitory effect of 8-OH-DPAT and attenuated the inhibitory effect on the somatosympathetic reflex. 8-OH-DPAT injected in the RVLM did not affect baroreceptor or chemoreceptor reflexes. Our findings suggest that activation of 5-HT1A receptors in the RVLM exerts a potent, selective inhibition on the somatosympathetic reflex.

scholarly journals The effect of metal ions on the activity and thermostability of the extracellular proteinase from a thermophilic Bacillus, strain EA.1

1992 ◽  
Vol 287 (2) ◽  
pp. 367-374 ◽  
Author(s):  
T Coolbear ◽  
J M Whittaker ◽  
R M Daniel
Keyword(s):  
Metal Ions ◽  
Calcium Ions ◽  
Inhibitory Effect ◽  
Decay Kinetics ◽  
Ionic Radii ◽  
Thermophilic Bacillus ◽  
Bacillus Strain ◽  
Bivalent Cations ◽  
Maximum Stability

The proteinase from the extremely thermophilic Bacillus strain EA.1 exhibits maximum stability at a pH of approx. 6.5. In the presence of calcium ions the half-life at 95 degrees C of the enzyme at this pH was 17 min, and loss of activity followed first-order decay kinetics. The role of metal ions in the activity and stability of the enzyme was studied using the holoenzyme, the metal-depleted apoenzyme, and a zinc-enriched apoenzyme preparation. Zinc and calcium ions were the preferred bivalent cations for the active site and stabilization site(s) respectively. Stabilization by metal ions was not in itself a highly stringent process, but ions other than calcium which stabilized the enzyme generally had a concomitant inhibitory effect on activity. Inhibition and stabilization of the enzyme by cations were concentration-dependent effects and certain ions activated the apoenzyme but not the holoenzyme. Manganese(II) ions conferred some stability and also activated the enzyme, but in the latter case were not as effective as zinc ions. The results are discussed with reference to the ionic radii, co-ordination number and preferred ligand donors of the ions. Mercury(II) ions severely compromised enzyme activity and stability, and the effects of thiol-reactive agents suggest that thiol groups also have a role in enzyme integrity.

Gastroduodenal mucus bicarbonate barrier: protection against acid and pepsin

2005 ◽  
Vol 288 (1) ◽  
pp. C1-C19 ◽  
Author(s):  
Adrian Allen ◽  
Gunnar Flemström
Keyword(s):  
Ph Gradient ◽  
Support Surface ◽  
First Line ◽  
Physiological Conditions ◽  
Neutral Ph ◽  
Primary Function ◽  
Gel Layer ◽  
Mucus Gel ◽  
And Control

Secretion of bicarbonate into the adherent layer of mucus gel creates a pH gradient with a near-neutral pH at the epithelial surfaces in stomach and duodenum, providing the first line of mucosal protection against luminal acid. The continuous adherent mucus layer is also a barrier to luminal pepsin, thereby protecting the underlying mucosa from proteolytic digestion. In this article we review the present state of the gastroduodenal mucus bicarbonate barrier two decades after the first supporting experimental evidence appeared. The primary function of the adherent mucus gel layer is a structural one to create a stable, unstirred layer to support surface neutralization of acid and act as a protective physical barrier against luminal pepsin. Therefore, the emphasis on mucus in this review is on the form and role of the adherent mucus gel layer. The primary function of the mucosal bicarbonate secretion is to neutralize acid diffusing into the mucus gel layer and to be quantitatively sufficient to maintain a near-neutral pH at the mucus-mucosal surface interface. The emphasis on mucosal bicarbonate in this review is on the mechanisms and control of its secretion and the establishment of a surface pH gradient. Evidence suggests that under normal physiological conditions, the mucus bicarbonate barrier is sufficient for protection of the gastric mucosa against acid and pepsin and is even more so for the duodenum.

scholarly journals The role of link-protein in the structure of cartilage proteoglycan aggregates

1979 ◽  
Vol 177 (1) ◽  
pp. 237-247 ◽  
Author(s):  
T E Hardingham
Keyword(s):  
Analytical Ultracentrifugation ◽  
Free Form ◽  
Link Protein ◽  
Physiological Conditions ◽  
Neutral Ph ◽  
Laryngeal Cartilage ◽  
Cartilage Proteoglycan ◽  
Proteoglycan Aggregates

Proteoglycan fractions were prepared from pig laryngeal cartilage. The effect of link-protein on the properties of proteoglycan-hyaluronate aggregates was examined by viscometry and analytical ultracentrifugation. Aggregates containing link-protein were more stable than link-free aggregates at neutral pH, at temperatures up to 50 degrees C and in urea (up to 4.0M). Oligosaccharides of hyaluronate were able to displace proteoglycans from link-free aggregates, but not from the link-stabilized aggregates. Both types of aggregate were observed in the ultracentrifuge, but at the concentration investigated (less than 2 mg/ml) the link-free form was partially dissociated and the proportion aggregated varied with the pH and temperature and required more hyaluronate for saturation than did link-stabilized aggregate. The results showed that link-protein greatly strengthened the binding of proteoglycans to hyaluronate and suggest that under physiological conditions it ‘locks’ proteoglycans on to the hyaluronate chain.

A vH+-ATPase is present in cultured sheep ruminal epithelial cells

2006 ◽  
Vol 291 (6) ◽  
pp. G1171-G1179 ◽  
Author(s):  
Benjamin Etschmann ◽  
Katrin Sophie Heipertz ◽  
Annabelle von der Schulenburg ◽  
Monika Schweigel
Keyword(s):  
Epithelial Cells ◽  
Primary Cultures ◽  
Selective Inhibition ◽  
Protein Band ◽  
Inhibitory Effect ◽  
B Subunit ◽  
Initial Ph ◽  
Acid Load ◽  
Acid Loading

In this study, the existence and functional activity of a vacuolar-type H+-ATPase (vH+-ATPase) was explored in primary cultures of sheep ruminal epithelial cells (REC). The mRNA transcripts of the E and B subunits of vH+-ATPase were detectable in RNA from REC samples by RT-PCR. Immunoblotting of REC protein extractions with antibodies directed against the B subunit of yeast vH+-ATPase revealed a protein band of the expected size (60 kDa). Using the fluorescent indicator BCECF and selective inhibitors (foliomycin, HOE 694, S3226), the contribution of vH+-ATPase and Na+/H+ exchanger (NHE) subtype 1 and 3 activity to the regulation of intracellular pH (pHi) was determined in nominally HCO3−-free, HEPES-buffered NaCl medium containing 20 mM of the short-chain fatty acid butyrate as well as after reduction of the extracellular Cl− concentration ([Cl−]e) from 136 to 36 mM. The initial pHi of REC was 7.4 ± 0.1 in nominally HCO3−-free, HEPES-buffered NaCl medium and 7.0 ± 0.1 after acid loading with butyrate. Selective inhibition of the vH+-ATPase with foliomycin decreased pHi by 0.19 ± 0.03 pH units. On the basis of the observed decreases in pHi resulting from inhibition of vH+-ATPase as well as of subtypes 1 and 3 of NHE, vH+-ATPase activity appears to account for ∼30% of H+ extrusion, whereas the activities of NHE subtypes 3 and 1 account for 20 and 50% of H+ extrusion, respectively. Lowering of [Cl−]e induced a pHi decrease (−0.51 ± 0.03 pH units) and impaired pHi recovery from butyrate-induced acid load. Moreover, reduction of [Cl−]e abolished the inhibitory effect of foliomycin and markedly reduced the HOE 694- and S3226-sensitive components of pHi, indicating a role of Cl− in the function of these H+ extrusion mechanisms. We conclude that a vH+-ATPase is expressed in ovine REC and plays a considerable role in the pHi regulation of these cells.

Role of Metal Ion in Specific Recognition of Pyrophosphate Ion under Physiological Conditions and Hydrolysis of the Phosphoester Linkage by Alkaline Phosphatase

2013 ◽  
Vol 52 (19) ◽  
pp. 11034-11041 ◽  
Author(s):  
Priyadip Das ◽  
Nellore Bhanu Chandar ◽  
Shishir Chourey ◽  
Hridesh Agarwalla ◽  
Bishwajit Ganguly ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Metal Ion ◽  
Physiological Conditions ◽  
Specific Recognition ◽  
Hydrolysis Of

scholarly journals Evaluation of the role of inositol trisphosphate in IgE-dependent exocytosis

1990 ◽  
Vol 270 (3) ◽  
pp. 685-689 ◽  
Author(s):  
G Gat-Yablonski ◽  
R Sagi-Eisenberg
Keyword(s):  
Inositol Trisphosphate ◽  
Close Correlation ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Physiological Conditions ◽  
Similar Range ◽  
Ige Mediated ◽  
Dose Dependent ◽  
Basophilic Leukemia

A close correlation exists between inhibition by 12-O-tetradecanoylphorbol 13-acetate (TPA) of inositol trisphosphate (InsP3) formation and the rise in internal Ca2+ concentrations in IgE-stimulated rat basophilic leukemia (RBL-2H3) cells. Inhibition of both processes is dose-dependent, with half-maximal and maximal inhibition occurring at 1.5 and 10 ng of TPA/ml respectively. At a similar range of concentrations TPA does not inhibit, but rather enhances, IgE-dependent secretion. When added to antigen-activated cells. EGTA immediately abrogates secretion and stimulates InsP3 production. In contrast, EGTA has only a small inhibitory effect on IgE-induced secretion from TPA-activated cells. In antigen-activated cells, EGTA partially inhibits InsP1 formation, suggesting that, unlike InsP3, InsP1 may in part be formed directly from phosphatidylinositol in a Ca2(-)-dependent manner. Together, these findings suggest that under physiological conditions the stimulated formation of InsP3 is insufficient for triggering secretion, and that Ca2+ influx is essential. Moreover, InsP3 formation is not obligatory for IgE-mediated exocytosis, provided that the cells are activated by TPA. Secretion from TPA-activated cells, which is independent of InsP3 formation and the rise in internal Ca2+, does not require the presence of external Ca2+, implying that the presence of external Ca2+ during IgE-induced secretion is required for producing the Ca2+ signal and not for exocytosis per se.

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