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Biomedical subjects

E J Simon

Publications and source records attributed to E J Simon.

At least 145 records · Page 8Linked to original sources
PubMed1978

Effect of morphine analogues on chemotaxis in Escherichia coli.

Pretreatment of Escherichia coli w3110 with levorphanol, a morphine analogue, reduced chemotaxis to serine, aspartic acid and galactose. This decreased chemotaxis was not due to decreased viability or motility. Pretreatment with 1.1 mM-levorphanol for 1 h, followed by washing to remove the drug prior to determination of chemotaxis, inhibited chemotaxis to each of the attractants by at least 80%. Pretreatment with dextrorphan, the enantiomorph of levorphanol, or levallorphan, the N-allyl analogue of levorphanol, resulted in a similar inhibition of chemotaxis. Reversal of the inhibition produced by pretreatment with levorphanol required a period of growth of at least one generation time.

Aspartic Acid↗
PubMed1978

[Opiate receptors and endorphins at the central nervous system level].

Four years ago, sterospecific sites for the bending of opiates were discovered within the brain of animals and the human being. All of the properties of these sites are in conformity with the proposition that they are pharmacological receptors which have long been postulated for these drugs. The binding of morphine or of one of its derivatives to these sites should result in chemical or physical reactions leading to well known pharmacological responses. These reactions following the binding of drugs to the receptors are not yet known, but there is some evidence that cyclical nucleotides play a role. The affinity of a whole series of morphine derivatives, agonists and atagonists, is well correlated with their pharmacological effectiveness. In the presence of sodium salts, antagonists become more strongly bound and agonists less strongly than in the absence of sodium. The evidence is presented. This is explained by an equilibrium between two formations of the receptor: one characteristic of the absence of sodium and one of its presence. Receptors are found in the nervous system of all vertebrates and their distribution has been studied in the human brain. The regions with the highest concentration of receptors are those of the limbic system. A high level exists also in the "substantia gelatinosa" of the spinal cord, which is involved in the passage of painful messages. Study of the function of morphine receptors has led to the isolation, in animal brain, of a number of peptides with morphine properties named endorphines. The first two endorphines isolated were pentapeptides named encephalins. The properties of endorphines from the subject of several lecture in this course.

Animals↗
PubMed1977

Receptor affinity and pharmacological potency of a series of narcotic analgesic, anti-diarrheal and neuroleptic drugs.

A series of 26 drugs was tested for in vitro binding to opiate receptors in the presence and absence of 0.1 M NaCl. The results were correlated with assays for in vivo pharmacological potency. Highly significant correlation was found between binding in the presence and absence of sodium ions and analgesic potency. For 10 drugs tested for anti-diarrheal potency significant correlation was observed with binding to brain opiate receptors when binding was carried out in sodium-containing medium. These data add support to the hypothesis that stereospecific opiate binding sites are pharmacological receptors which mediate analgesia and anti-diarrheal action. We found that neuroleptics can bind to opiate receptors with affinities in the micromolar range, in agreement with reports by others. The anti-diarrheal compound loperamide exhibits no significant central opiate effects but binds to opiate receptors from brain in vitro with high affinity. Evidency is presented suggesting that the lack of specific analgesic effect is the result of poor penetration through the blood--brain barrier. Our results lend further support to the similarity of opiate receptors in the brain and in the intestinal tract.

Analgesics, Opioid↗
PubMed1977

Analysis of electrical noise in turtle cones.

1. Properties of the light-sensitive voltage noise in cones in the retina of the turtle, Pseudemys scripta elegans, have been studied by intracellular recording.2. Suppression of the noise by light was a function of the hyperpolarizing response of a cone but not of the size or pattern of illumination.3. Power density spectra of the noise were fitted in many cones by the product of two Lorentzians with characteristic time constants tau(1) and tau(2) averaging 40 and 7 msec respectively. The spectra of some cells were peaked and could be fitted by a resonance curve.4. Spectra in dim light exhibited decreased low frequency power. They could often be fitted by a product of two Lorentzians using the same value of tau(2) as used in darkness but decreasing tau(1) and the zero frequency asymptote. An e-fold reduction in tau(1) occurred with lights which hyperpolarized by 4-7 mV.5. Injection of hyperpolarizing currents of about 0.1-0.2 nA into weakly coupled cones reduced the noise, and also reduced the sensitivity to dim flashes.6. The variance-voltage relation during steady illumination of different intensities differed from cone to cone. Dim lights increased the noise in some cells and decreased it in others, but moderately bright lights which gave steady responses of more than about one third maximal reduced the noise in all cells.7. When the cell was transiently depolarized during the differentiated component following steady illumination, the noise was less than it was after prolonged darkness.8. In the after-effect of bright light, the time course of recovery of noise was the same as that of flash sensitivity and voltage. The noise was reduced e-fold for hyperpolarizations averaging 3 mV while for sensitivity this reduction occurred for 1.3 mV. For a given hyperpolarization the noise was lower during the after-effect than during steady dim illumination.9. When a series of dim flashes was delivered to a cone, no significant increase in variance over the dark noise was detected during the photo-response. This implies that each photoisomerization evokes no more than about 1.5 muV at the peak of the response in a coupled cone, corresponding to about 50 muV in an isolated cone.10. The elementary shot events underlying the noise are about 100 muV in amplitude in an isolated cone, have a characteristic time constant of 16-60 msec and reflect unit conductance fluctuations of about 16 pS (S, Siemen identical with Omega(-1)).11. It is concluded that the noise source is internal to the cones. We postulate that the noise arises from opening and closing of the light-sensitive ionic channels in the outer segment, and that in darkness there is a residual concentration of the blocking substance which on average closes up to about one third of the channels. It seems likely that the unit event involves a considerable number of blocking molecules and ionic channels.

Action Potentials↗
PubMed1977

The purification of antimorphine antibodies by affinity chromatography.

Affinity chromatography was employed successfully to purify extensively antimorphine antibodies produced in rabbits. Morphine succinylated at position 6 was attached to bovine serum albumin to make it immunogenic and to Sepharose beads for affinity chromatography. A crude gamma-globulin fraction of antimorphine serum, prepared by salt fractionation, was used for purification. After unbound gamma-globulin was washed off the column with phosphate-buffered saline, two populations of antimorphine antibodies were eluted in succession by two low pH buffers. Each of these two purified antibody fractions had an index of heterogeneity of approximately 1. Immunoelectrophoresis indicated that the antibodies were immunoglobulin G and that they formed a single precipitation band with antirabbit serum. The average association constants for morphine of the two purified antibody fractions were similar and ranged from 4.5 to 4.8 X 10(7) LITERS/MOL-1. A 67-fold purification of the antimorphine antibodies could be achieved by a single pass through an affinity column.

Antibodies↗
PubMed1976

The relation between intercellular coupling and electrical noise in turtle photoreceptors.

1. Intracellular recordings from cones and rods in the retina of the turtle, Pseudemys scripta elegans, revealed that in darkness the cell voltage fluctuated spontaneously about its mean level. The fluctuations were reduced during bright steady illmination of the cell often to a level close to that obtained with the electrode outside the cell where the noise did not change significantly during illumination. 2. The magnitude of the intrinsic dark noise (voltage variance in darkness minus voltage variance in strong light) varied widely from cell to cell. In the noisiest cones it was about 0-4 mV2 while in quiet cones it was often as low as 0-01 mV2. The noise appeared radom and could be fitted by a Gaussian probability density function. 3. The spread of voltage in the network of coupled photoreceptors was estimated by measuring the spatial profile of the response to a brief flash of constant intensity moved across the retina. For a light stimulus in the form of a long narrow slit, the peak flash response usually decayed exponentially with displacement from the centred position. 4. For maximum responses less than about 5 mV in cones, the length constant of exponential decay, lambda, varied from less than 10 mum to greater than 35 mum, and the values obtained in opposite directions were often unequal. Background illumination did not significantly change lambda. In cells with extremely narrow spatial profiles, an exponential fit to the decay could not be made reliably. 5. Occasionally the spatial profiles had definite secondary peaks. In the most pronounced examples in a red-sensitive cone and in a rod the maxima were separated by about 20 and 50 mum respectively; for each, one peak was approximately as sharp as the optical stimulator while the second was broader. 6. Cones with short length constants displayed high dark noise while cones with long length constants were relatively quiet. 7. Three models of electrical coupling between cells were investigated: one based on a distributed network, one on a discrete square grid arrangement, and one on a discrete hexagonal array. Each model predicts a strong dependence of both noise and input resistance on length constant, and for tightly coupled cells each predicts that voltage variance is proportional to lambda-2. 8. The measured relationship between voltage variance and lambda in a large sample of cones was well described by both discrete models when the average cell spacing was taken to be approximately 15 mum. 9...

Animals↗
PubMed1975

Solubilization of a stereospecific opiate-macromolecular complex from rat brain.

A [3H]etorphine-macromolecular complex has been solubilized from rat brain synaptosomal fraction by extraction with the nonionic detergent Brij 36T. Stereospecificity of binding to this solubilized complex was demonstrated by the finding that radioactivity in the complex was virtually eliminated when binding had occurred in the presence of excess levorphanol, an active narcotic analgesic, while it was unaffected by its inactive enantiomorph dextrorphan. Bound radioactivity was dissociated by proteolytic enzymes, sulfhydryl reagents, and heat, suggesting the presence of protein. The bound solubilized macromolecular moiety may be the opiate receptor.

Animals↗