Search PubMed⌕ Search

Biomedical subjects

R Simantov

Publications and source records attributed to R Simantov.

At least 109 records · Page 6Linked to original sources
PubMed1978

The opiate receptor binding interactions of 3H-methionine enkephalin, an opioid peptide.

3H-Methionine enkephalin binds stereospecifically with high affinity to opiate receptors in rat brain membranes. Equilibrium experiments indicate two distinct dissociation constants with KD values of 1.8 and 5.8 nM respectively. 3H-Methionine enkephalin associates and dissociates from the opiate receptor with 8--10 fold slower kinetics than 3H-opiates. Though several opiates have similar affinities for sites labeled by 3H-methionine enkephalin, 3H-dihydromorphine and 3H-naloxone, some opiates such as morphine, dihydromorphine and oxymorphone are only one tenth as potent in competing for 3H-methionine enkephalin as for 3H-dihydromorphine and 3H-naloxone binding. As with other opiate agonists, 5--10 mM sodium selectively decreases the binding of 3H-methionine enkephalin. At 26 degrees C, 0.1--1.0 mM manganese but not magnesium or calcium increases the binding of 3H-methionine enkephalin, while at 0 degrees C manganese decreases the binding of methionine enkephalin.

Animals↗
PubMed1978

Differential desensitization of functional adrenergic receptors in normal and malignant myeloid cells: relationship to receptor-mediated hormone cytotoxicity.

Malignant myeloid leukemic cells and normal macrophages and granulocytes have functional beta-adrenergic receptors, which have been quantitated by radioreceptor binding with the beta-adrenergic antagonist [(3)H]dihydroalprenolol and by induction of cyclic AMP by adrenergic hormones. Both the normal and leukemic cells have beta(2)-adrenergic receptors, and the [(3)H]dihydroalprenolol binding was saturable, reversible, and stereospecific. The leukemic cells consisted of clones that could be induced to differentiate (MGI(+)D(+)) and clones that could not be induced to differentiate to mature macrophages and granulocytes by the protein inducer MGI. The different types of leukemic clones all had 1100-2300 receptor sites per cell, whereas normal macrophages had 7000 receptors per cell. The differentiation of MGI(+)D(+) leukemic cells was associated with an increase in receptors to a number similar to that found with normal macrophages. MGI(+)D(+) leukemic cells and normal macrophages were able to densensitize to the beta-adrenergic agonist (-)isoproterenol, shown by termination of cyclic AMP induction within 10-15 min and the lack of a second induction. The leukemic cells that could not be induced to differentiate lacked this capacity for desensitization, possibly due to an alteration in the uncoupling system between the receptor and adenylate cyclase. The lack of desensitization in these leukemic cells was associated with a higher sensitivity to the receptor-mediated cytotoxic effects of adrenergic hormones. It is suggested that cells, like some leukemic cells, that are unable to desensitize to adrenergic and possibly other hormones may be appropriate targets for differential destruction by hormones under conditions that do not affect normally desensitizing cells.

Adenylyl Cyclases↗
PubMed1977

Enkephalin: radioimmunoassay and radioreceptor assay in morphine dependent rats.

A sensitive and specific radioimmunoassay for enkephalins is described which discriminates between leucineenkephalin and methionine-enkephalin. Total opioid peptide activity was assayed by the ability of brain extracts to compete for opiate receptor binding. In rats treated with morphine and/or naloxone, opiates were separated from opioid peptides by Dowex AG-50W column chromatography prior to radioreceptor assay. Chronic administration of morphine failed to alter immunoreactive enkephalin levels or total opioid activity in radioreceptor assays.

Animals↗
PubMed1977

A morphine-like factor in mammalian brain: analgesic activity in rats.

A partially purified morphine-like peptide 'enkephalin' (PPE) extract from bovine brain elicited pronounced apparent analgesia after injection into the periaqueductal gray matter of rat brain. This analgesia was reversed by the opiate antagonist naloxone in a dose-dependent fashion. Analgesia was more rapid in onset and much shorter in duration after PPE than after morphine administration. Analgesia was elicited only by those ion exchange column fractions of PPE that competed potently for opiate receptor binding. No analgesia could be detected when PPE or morphine injections were administered at a site 2 mm lateral to the periaqueductal gray matter. The potencies of synthetic methionine- and leucine-enkephalin in eliciting analgesia were less than 1% of those of partially purified enkephalin extracts when doses of equivalent ability to compete for opiate receptor binding were compared.

Analgesics↗
PubMed1977

Opioid peptide enkephalin: immunohistochemical mapping in rat central nervous system.

Using specific antisera to methionine-enkephalin and leucine-enkephalin, we have visualized apparent enkephalin-containing neuronal fibers and terminals throughout the central nervous system of the rat. Immunoreactive enkephalin displays sharply defined localizations. Regions of highest immunofluorescent density include the laminae I and II of the spinal cord, the substantia gelatinosa of the caudal nucleus of nerve V, the vagal nuclei of the medulla, the periventricular and periaqueductal areas of the upper medulla and midbrain, dorsomedial thalamic regions, specific hypothalamic nuclei, the basal ganglia, particularly the globus pallidus and the central nucleus of the amygdala, and the lateral septum. In certain regions enkephalin immunofluorescence corresponds closely with the distribution of autoradiographic opiate receptor grains.

Amygdala↗