Search PubMed⌕ Search

Biomedical subjects

R S Turner

Publications and source records attributed to R S Turner.

72 records · Page 4Linked to original sources
PubMed1983

Cobra polypeptide cytotoxin I and marine worm polypeptide cytotoxin A-IV are potent and selective inhibitors of phospholipid-sensitive Ca2+-dependent protein kinase.

The effects of a number of polypeptide cytotoxins and neurotoxins on various protein kinases were examined. It was found that cobra cytotoxin I and marine worm cytotoxin A-IV effectively and specifically inhibited phospholipid-sensitive Ca2+-dependent protein kinase (PL-Ca-PK) relative to myosin light chain kinase and cyclic nucleotide-dependent protein kinases. Inhibition of PL-Ca-PK by these cytotoxins could be overcome by phosphatidylserine. Neurotoxins, in comparison, were much less effective inhibitors. The present findings indicated that these polypeptide cytotoxins, unlike other agents reported to date, were selective inhibitors of PL-Ca-PK and could be used to differentiate Ca2+-dependent events regulated by phospholipid or calmodulin.

Bee Venoms↗
PubMed1982

Inhibition by melittin of phospholipid-sensitive and calmodulin-sensitive Ca2+-dependent protein kinases.

Effects of melittin, an amphipathic polypeptide, on various species of protein kinases were investigated. It was found that melittin inhibited the newly identified phospholipid-sensitive Ca2+-dependent protein kinase (from heart, brain, spleen and neutrophils) and the cardiac myosin light-chain kinase, a calmodulin-sensitive Ca2+-dependent enzyme. In contrast, melittin had little or no effect on either the holoenzymes of the cardiac cyclic AMP-dependent and cyclic GMP-dependent protein kinases or the catalytic subunit of the former. Kinetic analysis indicated that melittin inhibited phospholipid-sensitive Ca2+-dependent protein kinase non-competitively with respect to ATP (Ki = 1.3 microM); although exhibiting complex kinetics, its inhibition of the enzyme was overcome by phosphatidylserine (a phospholipid cofactor), but not by protein substrate (histone H1) or Ca2+. On the other hand, melittin inhibited myosin light-chain kinase non-competitively with respect to ATP (Ki = 1.4 microM) or Ca2+ (Ki = 1.9 microM), and competitively with respect to calmodulin (Ki = 0.08 microM); although exhibiting complex kinetics, its inhibition of the enzyme was reversed by myosin light chains (substrate protein). The present findings indicate the presence of functionally important hydrophobic or hydrophilic loci on the Ca2+-dependent protein kinases, but not on the cyclic nucleotide-dependent class of protein kinase, with which melittin can interact. Moreover, the kinetic data suggest that melittin inhibited myosin light-chain kinase by interacting with a site on the enzyme the same as, or proximal to, the calmodulin-binding site, thus interfering with the formation of active enzyme-calmodulin-Ca2+ complex.

Adenosine Triphosphate↗
PubMed1982

Basic protein in brain myelin is phosphorylated by endogenous phospholipid-sensitive Ca2+-dependent protein kinase.

Phosphorylation of myelin basic protein (MBP) in rat or rabbit brain myelin was markedly stimulated by Ca2+, and this reaction was not essentially augmented by exogenous phosphatidylserine or calmodulin or both. Solubilization of myelin with 0.4% Triton X-100 plus 4 mM EGTA, with or without further fractionation, showed that Ca2+-dependent phosphorylation of MBP required phosphatidylserine, but not calmodulin. DEAE-cellulose chromatography of solubilized myelin revealed a pronounced peak of protein kinase activity stimulated by a combination of Ca2+ and phosphatidylserine; a protein kinase stimulated by Ca2+ plus calmodulin was not detected. These findings clearly indicate an involvement of phospholipid-sensitive Ca2+-dependent protein kinase in phosphorylation of brain MBP, although a possible role for the calmodulin-sensitive species of Ca2+-dependent protein kinase in this reaction could not be excluded or established. Phosphorylation of MBP in solubilized rat myelin catalyzed by the phospholipid-sensitive enzyme was inhibited by adriamycin, palmitoylcarnitine, trifluoperazine, melittin, polymyxin B, and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7).

Animals↗
PubMed1981

Protease-insensitive sea urchin embryo cell adhesions become protease sensitive in the presence of azide or cytochalasin B.

To understand the nature of the cell adhesions that must be modified during sea urchin embryo primary mesenchyme formation, we are studying the adhesive components of the hatched blastula stage embryo of Strongylocentrotus purpuratus. Pronase treatment conditions have been defined that leave the cells intact and able to recover from the effects of the protease upon its removal. Under these conditions, adhesion of the cells to tissue culture plates is totally eliminated, but cell-cell adhesion formation is only partially inhibited. Analysis of iodinated cell surface proteins indicates that most are affected by the pronase. Further studies of pronase effects found that sodium azide-treated cells are slightly adhesive and that pronase treatment of azide-treated cells totally eliminates cell-cell adhesions.

Animals↗
PubMed1981

Methionine-enkephalin and morphine: amount ejected microiontophoretically.

The microiontophoretic transport numbers of Met-enkephalin and morphine were determined by ejecting the tritiated compounds from both 5-barrel and 7-barrel micro-pipettes into a small volume of 0.9% NaCl, using a series of ejection currents and various timed durations. The transport number of Met-enkephalin was 2-4 times less than that for morphine in 5- and 7-barrel pipettes. The transport numbers of both drugs in 5-barrel pipettes were significantly greater than those in 7-barrel pipettes. These results indicate the need for caution in comparing the data derived from different studies that use microiontophoresis. The transport numbers for morphine and Met-enkephalin were used to compare the effects of these agents on neuronal firing.

Animals↗
PubMed1977

Hermann von Helmholtz and the empiricist vision.

The philosophical convictions of Hermann von Helmholtz and the empiricist psychology he developed have been extensively discussed in historical literature. This literature has not usually emphasized the tacti assumptions about human physiology that underlaid these convictions nor the way in which Helmholtz's epistemology served as a methodological directive in his research. Helmholtz assumed nerve transmission between sense organs and the mind to be a passive process. Distortion in stimulus patterns occurs physically in the sense organs, which can therefore be treated through mechanical analogies. Stimuli become converted to the perceptions of consciousness through mental processes that are essentially analogous to conscious, inductive inference and that are therefore susceptible, in principle, to introspective investigation. This view of mental function reflected Helmholtz's intellectual debt to German idealism, especially to the philosophical views of J.G. Fichte.

Germany↗
PubMed1975

A possible model for cell-cell recognition via surface macromolecules.

Alternative possibilities for the establishment of the proper cell distribution during embryogenesis are summarized at the beginning, followed by an assessment of the examples known so far where cell-cell recognition is known to be mediated via cell surface components. In the second part the species-specific recognition process which occurs during the sorting-out of dissociated sponge cells is analysed since it may serve as a possible model for cell-cell recognition in higher animals. Three possible mechanisms for the establishment of proper cell distribution are considered. These include, first, chemotaxis: secondly, guidance of cell or cell sheet movement by extracellular matrix or by surrounding cells and thirdly, random movement followed by recognition at the final point of destination. Recognition is necessary for both of the two latter processes, i.e. for cell guidance as well as for locking the cells into their final position after random movement. Two basically different recognition mechanisms should be distinguished from each other. On the one hand cells may recognize each other with the help of macromolecules situated in or just outside of the plasmamembrane which fit to each other like enzymes and substrates or antibodies and antigens. On the other hand, cells may exchange information by exchanging cytoplasmatic components via vesicles or gap junctions. The species-specific aggregation of dissociated sponge cells is considered to be a possible model for cell-cell recognition in higher animals. A proteoglycan-like intercellular macromolecule called aggregation factor seems to mediate recognition of a given species of cells in the reaggregation process of dissociated cells. The data available at the present time suggest that a monovalent surface macromolecule (baseplate) may mediate the recognition process probably by recognizing the carbohydrate side chains of the multivalent proteoglycan aggregation factor. A cell-free system was devised to mimic this aggregation process. Addition of aggregation factor to baseplate-coated sepharose beads of approximately the size of the original sponge cells has essentially the same characteristics as the cellular system. Macromolecule-coded surface information for the recognition between cells has not been established during the embryogenesis of higher animals and remains an interesting challenge.

Animals↗