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Biomedical subjects

D Allan

Publications and source records attributed to D Allan.

At least 163 records · Page 9Linked to original sources
PubMed1975

Recognition at cell surfaces: phytohaemagglutinin-lymphocyte interaction.

Many aspects of cell behaviour are regulated by the interaction of extracellular ligands with specific receptors exposed on the cell surface. The receptors correspond to membrane proteins and expecially glycoproteins. A key event in regulation is the transmission across the surface membrane of the information resulting from receptor-ligand interaction. The activation of lymphocytes by Phaseolus vulgaris phytohaemagglutinin (PHA) provides a convenient experimental model for the study of the molecular basis of receptor-ligand interaction and the molecular consequences of interaction. The receptor mediating lymphocyte activation by PHA is probably a unique glycoprotein which is present to the extent of about 3 X 10(4) molecules/cell. The PHA-receptor complex solubilized in 1% sodium deoxycholate has a molecular size of about 3 X 10(5). The primary event in the activation process is probably an increase in the permeability of the surface membrane to Ca2+. This may be achieved by PHA cross-linking ('patching') the receptors to form a polar channel that permits an influx of Ca2+.

Animals↗
PubMed1975

Enhanced synthesis de novo of phosphatidylinositol in lymphocytes treated with cationic amphiphilic drugs.

A variety of amphiphilic cations caused very large increases in the rates of incorporation of Pi and glycerol into phosphatidylinositol in pig mesenteric small lymphocytes. This synthesis de novo of phosphatidylinositol led to a doubling of the phosphatidylinositol concentration in the cells within 3.5 h. The increase in synthesis of phosphatidylinositol labelled with [3H]- or [14C]-glycerol was matched by an approximately equivalent decrease in incorporation of glycerol into phosphatidylcholine, phosphatidylethanolamine and triacylglycerol. Amphilic cations which produced these effects included, in order of decreasing effectiveness, trifluoperazine (half-maximal effect at about 70 mum) greater than chlorpromazine approximately promethazine approximately imipramine greater than cinchocaine greater than amethocaine approximately cetyltrimethylammonium greater than fenfluramine greater than amphetamine greater than 2-phenethylamine greater than cocaine approximately procaine; the most effective compounds were those with the largest and most hydrophobic non-polar substituents. The response to cations was not changed by varying the extracellular Ca2+ concentration in the range 10 nm-1mm. The active amphiphilic cations interacted with anionic phospholipids causing aggregation of aqueous dispersions and/or changes in chromatographic behaviour. These results indicate that amphiphilic cations redirect glycerolipid synthesis de novo, probably owing to inhibition of phosphatidate phosphohydrolase, so that phosphatidylinositol synthesis is increased at the expense of other glycerolipids.

Amphetamine↗
PubMed1974

Phosphatidylinositol cleavage catalysed by the soluble fraction from lymphocytes. Activity at pH5.5 and pH7.0.

Phosphatidylinositol breakdown by subcellular preparations of small lymphocytes from pig mesenteric lymph nodes was investigated. Activity was higher than in preparations from the tissues studied previously; it was recovered largely in the soluble fraction, which showed pH optima at both 5.4-5.6 and 7.0-7.3. As in other tissues, phosphatidylinositol cleavage produced 1,2-diacylglycerol and a mixture of myo-inositol 1:2-cyclic phosphate and myo-inositol 1-phosphate. It was stimulated by addition of CaCl(2) and, less effectively, by MgCl(2). On sucrose-density-gradient ultracentrifugation at pH7.0 two peaks of activity were observed (approx. sedimentation coefficients 8S and 10S); the activity profiles on the gradients were similar when assayed at pH7.0 and 5.5. Activity at pH7.0 (and 0.4mm-CaCl(2)) was decreased by agents, such as salts and lipophilic cations, which tend to neutralize the negative charge of phosphatidylinositol; at pH5.5 these agents slightly stimulated activity. It is suggested that the same enzyme(s) may be responsible for activity at both pH optima and that previous workers may have underestimated the pH7.0 activity because of the inhibitory influence of cations under the usual assay conditions.

Animals↗
PubMed1974

Phosphatidylinositol cleavage in lymphocytes. Requirement for calcium ions at a low concentration and effects of other cations.

The soluble activity in lymphocytes which converts phosphatidylinositol into 1,2-diacylglycerol and inositol phosphates requires Ca(2+) ions. At pH7 maximum activity occurs at [Ca(2+)](free) approximately 0.7mum whereas at pH5.5 the equivalent value is approx. 50mum. At [Ca(2+)](free) approximately 1mum, a concentration similar to common intracellular values, essentially all activity is confined to the peak of activity at pH7.0. Previous reports of requirements for larger amounts of Ca(2+) may reflect the fact that the Ca(2+)-buffering capacity of phosphatidylinositol means that high substrate concentrations can effectively decrease [Ca(2+)](free). Cations which displace Ca(2+) from association with phosphatidylinositol can, at low [Ca(2+)](free), enhance enzyme activity. Phosphatidylinositol breakdown in intact cells might be controlled, at least in part, by changes in intracellular [Ca(2+)](free).

Animals↗