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M Mezna

Publications and source records attributed to M Mezna.

25 records · Page 2Linked to original sources
PubMed1995

Pharmacological modulators of the inositol 1,4,5-trisphosphate receptor.

Elevation of cytosolic calcium concentrations, induced by many neurotransmitters, plays a crucial role in neuronal function. Some neurotransmitters produce the second messenger InsP3 which activates an intracellular calcium channel (InsP3 receptor) usually located in the endoplasmic reticulum. This article undertakes a comprehensive survey of most pharmacological modulators of the InsP3 receptor so far reported. This review discusses in detail competitive antagonists, non-competitive antagonists and thiol reactive reagents, highlighting their modes of action and in some cases indicating drawbacks in their use.

Adenosine Triphosphate↗
PubMed1994

Zinc and barium inhibit the phospholipase A2 from Naja naja atra by different mechanisms.

The mode of inhibition of the phospholipase A2 (PLA2) enzyme from the Chinese cobra (Naja naja atra) by Zn2+ is qualitatively different from inhibition by Ba2+. Inhibition by Ba2+ shows the kinetic characteristics of a conventional competitive inhibitor acting to displace Ca2+ from a single essential site, but Zn2+ has the paradoxical property of being more inhibitory at high than at low Ca2+ concentration. Kinetic analysis of the Ca(2+)-dependence of enzymic activity shows a bimodal response, indicating the presence of two Ca(2+)-binding sites with affinities of 2.7 microM and 125 microM respectively, and we propose that these can be identified with the two Ca(2+)-binding sites revealed by crystallographic analysis [White, Scott, Otwinowski, Gleb and Sigler (1990) Science 250, 1560-1563]. The results are consistent with the model that the enzyme is activated by two Ca2+ ions, one that is essential and can be displaced by Ba2+, and one that modulates the activity by a further 5-10-fold and which can be displaced by Zn2+. An alternative model is also presented in which the modulating Zn(2+)-binding site is a phenomenon of the lipid/water interface.

Barium↗
PubMed1994

Conductimetric assays for the hydrolase and transferase activities of phospholipase D enzymes.

Measurement of solution electrical conductance (conductimetry) is a simple direct assay method for the protogenic, hydrolytic reactions catalyzed by all phospholipase enzymes. The technique is especially suitable for assay of phospholipase D (PLD) enzymes where cleavage of zwitterionic substrates reinforces the pH dependent conductance change and allows the method to be used over a much wider pH range than the equivalent titrimetric assay. The ability to detect zwitterion cleavage enables the method to assay reactions in which phospholipase D transfers neutral, or anionic, alcohol species to the zwitterionic substrates phosphatidyl choline and phosphatidyl ethanolamine. The method can follow the sequential attack by different phospholipases and provides a simple technique for investigating the effect of substrate structure on susceptibility to various phospholipase enzymes. The results confirm that PLD from Streptomyces chromofuscus can attack lysophospholipids, but cannot transfer primary alcohols to the phosphatidyl residue, while the PLD from savoy cabbage is an efficient transferase, but cannot attack lysophospholipids. The data suggest that the bacterial PLD fails to act as a transferase because it hydrolyzes the transphosphatidylation products. Some phosphatidyl alcohols are more highly susceptible to PLA2 attack than the parent phosphatidyl choline derivatives.

Animals↗
PubMed1994

Addition-order dependent modulation of the sensitivity of rabbit erythrocyte membrane to bee venom phospholipase A2 by oleic acid, lysophosphatidyl choline and albumin.

The addition of exogenous oleic acid to erythrocyte membranes induces a characteristic membrane crenation and sensitises the cells to the lytic action of phospholipase A2 enzymes. Both effects are extremely sensitive to inhibition by endogenous lysophosphatidyl choline (LPC), but the strength of inhibition depends of the order in which the reagents are added to the cells. These responses are further enhanced when the reagents are extracted from the cell membranes by treatment with albumin. Thus the inhibitory action of LPC added before oleic acid increases when the reagents have been extracted but that of LPC added after oleic acid decreases after extraction. The results are discussed in terms of the stimulation of PLA2 activity by enhanced membrane curvature.

Albumins↗