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Biomedical subjects

R Wade

Publications and source records attributed to R Wade.

At least 73 records · Page 4Linked to original sources
PubMed1982

CGS 8216: receptor binding characteristics of a potent benzodiazepine antagonist.

CGS 8216 is a novel nonbenzodiazepine that inhibited 3H-flunitrazepam (3H-FLU) binding to rat synaptosomal membranes in vitro at subnanomolar concentrations. It prevented the in vivo labeling of brain benzodiazepine receptors by 3H-FLU with the same potency as diazepam when given orally to mice. Pharmacologic tests showed that it was devoid of benzodiazepine-like activity but it antagonized the actions of diazepam in these tests. It did not interact with alpha- or beta- adrenergic, H1-histaminergic or GABA receptors but it inhibited adenosine-activation of cyclic AMP formation. Studies with 3H-CGS 8216 demonstrated that it bound specifically and with high affinity to rat forebrain membranes and was displaced by drugs with an order of potencies similar to that observed when 3H-diazepam and 3H-FLU were used as radioligands. The regional distribution of 3H-CGS 8216 binding sites in the brain was also similar to that of 3H-FLU. Dissociation of 3H-CGS 8216 binding was slow at 0 degrees C but increased with temperature and was almost complete within 1 min at 37 degrees C. Scatchard analyses were linear, yielding KD values of 0.044, 0.11 and 0.18 nM at 0, 25 and 37 degrees C, respectively; the Bmax value did not change appreciably with temperature and was approximately 1000 fmoles/mg protein. Using 3H-FLU, the value for Bmax as well as for the KD increased with temperature. The total number of binding sites determined for 3H-FLU was greater than that for 3H-CGS 8216 at each temperature. CGS 8216 exhibited mixed-type inhibition of 3H-FLU binding. GABA did not stimulate 3H-CGS 8216 binding whereas it enhanced 3H-FLU binding. CGS 8216 may be a useful ligand for probing the antagonist properties of the benzodiazepine receptor and is likely to exhibit interesting therapeutic effects.

Animals↗
PubMed1982

Tritiated peptides. 12. Synthesis and biological activity of [4-3H-Phe8]substance P.

Substance P has been prepared 3H labeled at Phe8 by catalytic deiodination of a protected precursor. Synthesis of the precursor was by solid-phase methodology on polydimethylacrylamide resin and by condensation in solution of fragments covering sequences 1-4, 5-7, and 8-11. Free peptide made by each route analyzed satisfactorily and had the same chromatographic characteristics as unlabeled substance P. It was indistinguishable from the latter by radioimmunoassay when N and C terminally directed antisera were used and in the ability to cause contractions of isolated guinea pig ileum. Specific radioactivity was 23 Ci/mmol.

Amino Acids↗
PubMed1982

The evolution of occupational health and the role of government.

Concern for the protection of workers' health is not new to medicine. Physicians in the 1400's raised awareness among colleagues as to the need to prevent the diseases of employment in mines. Society has responded to increasing levels of evidence as to the relationships between disease and certain worksites by making employers accountable for the individual and social costs incurred by poor workplace hygiene. This has occurred by the development of workers' compensation and occupational health and safety regulatory programs. The impact of these efforts has been to significantly reduce occupational disease and safety problems in industry. Increasing resources have also been given to the training of physicians in occupational medicine and research into links between occupations and disease. Increasing pressure to reduce public spending and to deregulate are challenging government's ability to continue research, training, technical information distribution, consultation and regulatory cleanup efforts to improve work conditions and thus reduce the incidence of occupational safety and health problems.

Government↗
PubMed1980

Specific binding of 3H-substance P to rat brain membranes.

The undecapeptide substance P is a putative neurotransmitter in the mammalian central nervous system (CNS), and may be associated with pain fibres in the spinal cord. Radiolabelled derivatives of other neuropeptides have been used to demonstrate specific interactions with receptor sites on brain membranes, and this approach has now been explored with substance P. We have now prepared [4-3H-Phe8]-substance P and we find that it binds reversibly to a saturable population of sites in rat brain particulate fractions. Scatchard analysis of concentration-dependent saturation of binding indicates a single population of non-interacting sites with a high affinity (Kd=0.38 nM) and a low density (Bmax=27.2 fmol per mg protein). Kinetic analyses indicate an apparent dissociation equilibrium constant of 0.46 nM. A variety of neurotransmitter amines and amino acids, and other peptides do not compete at the substance P sites, but structurally related peptides or shorter C-terminal fragments of substance P are active. The rank order of potency of these substance P-related peptides agrees with that reported for their effects in depolarizing spinal cord neurones. The regional distribution of the specific binding sites for 3H-substance P parallels that of substance P immunoreactivity, being high in the hypothalamus and low in the cerebellum and cerebral cortex. The characteristics of the 3H-substance P binding sites are consistent with those expected for substance P receptors.

Animals↗