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Biomedical subjects

R Simantov

Publications and source records attributed to R Simantov.

At least 91 records · Page 5Linked to original sources
PubMed1982

Enhancement of hormone action by a phorbol ester and anti-tubulin alkaloids involves different mechanisms.

The tumor-promoting phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA) enhanced 1-isoproterenol and prostaglandin E1 stimulated cyclic AMP formation in clones of mouse myeloid leukemic cells. The enhancement was found up to 3h after TPA treatment and had disappeared after 24h, indicating its reversibility. The effect of TPA was not inhibited by removal of extracellular Ca2+ or pre-treatment with the calcium ionophore A23187. This enhancement by TPA seems to involve a different pathway than enhancement of response to the same hormones after treatment with the anti-tubulin alkaloids colchicine or vinblastine, since a myeloid leukemic cell mutant clone that was non-responsive to the anti-tubulin alkaloids responded to TPA. Furthermore, combined treatment of colchicine-sensitive cells with TPA and colchicine showed an additive stimulating effect. The enhancement of cell response to hormones by TPA was found in myeloid leukemic cell clones that either were or were not induced to differentiate after treatment with TPA. This suggests that enhancement of the effect of these and possibly other hormones by TPA may be an initial step of TPA action, but that this enhancement is not sufficient to induce the wide repertoire of TPA effects including induction of differentiation.

Alprostadil↗
PubMed1982

Local electrographic effects of leu-enkephalin microinjections into the brain.

Microinjections of Leu-enkephalin were made in dorsal hippocampus, caudate nucleus, amygdala, nucleus accumbens and parietal cortex in rats. The effects of enkephalin on the local electrical activity recorded from the area of the microinjection are described. Depression effects (attenuation of amplitudes and slowing) were recorded in caudate nucleus, nucleus accumbens, amygdala and parietal cortex, but not in hippocampus. Activation and epileptiform effects (spikes, seizures) were recorded from all structures studied.

Animals↗
PubMed1982

Effects of acute and chronic morphine treatment of calmodulin activity of rat brain.

The cyclic AMP-phosphodiesterase assay was used to quantitate the amount of calmodulin activity in various brain areas of male rats treated acutely or chronically for 5 days with morphine. The acute treatment with morphine decreased calmodulin activity in the mitochondrial-synaptosomal P2 fraction of the striatum, midbrain, and thalamus but had no effect on the cerebellum, which contains a low density of opiate receptors. The decrease in calmodulin activity by morphine was dose-dependent and was blocked by the opiate antagonist naloxone. In contrast, chronic treatment of rats with morphine increased calmodulin activity in the mitochondrial-synaptosomal P2 of the striatum, midbrain, cerebral cortex, and thalamus. A highly sensitive Ca2+/Mg2+-ATPase assay was also used to quantitate the amount of calmodulin activity in subcellular fractions obtained from the striatum. Chronic morphine treatment caused a significant increase in calmodulin activity in the membrane containing microsomal, synaptosomal, and mitochondrial layers but only a small change in the layer that contained the soluble proteins and the synaptic vesicles. It is suggested that alteration of the content of calmodulin in specific subcellular sites may have a central role in opiate action and addiction via regulation of multiple calmodulin-sensitive biochemical pathways.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1981

Opiate receptor binding in the brain of the hypertensive rat.

Experimental and genetic hypertension in male rate is accompanied by a lower specific [3H]naloxone binding in the dorsal horn of the spinal cord, and in the hippocampus as compared to controls. Rats which are genetically resistant to hypertensive stimuli have a higher specific [3H]naloxone binding in the nucleus tractus solitarius and lower opiate receptor binding in the dorsal horn. Together with previous studies which demonstrated a correlation between blood pressure and pain sensitivity, these results support the notion that specific brain loci participate in co-regulation of pain perception and blood pressure.

Animals↗
PubMed1981

Sexual behavior decreases pain sensitivity and stimulated endogenous opioids in male rats.

In male rats copulation has antinociceptive effects as measured either by shock-induced vocalizations or hindlimb withdrawal to pinch. Prolonged mating reduces the content of endogenous opioids in midbrain but not in hypothalamus or caudate nucleus. Blockage of opiate receptors with the narcotic antagonist naloxone (4 mg/kg) significantly extends the postejaculatory interval. The results indicate that mating is a biological stimulus for the release of endogenous opoids, possibly to (a) prevent intense sexual stimulation from becoming aversive, and (b) increase its reward value.

Analgesia↗
PubMed1981

Influence of body temperature on the epileptogenic effect of enkephalin microinjections into the hippocampus.

The influence of different body temperatures on the epileptiform discharges induced in hippocampus by local microinjections of leu-enkephalin was studied in rats. In the absence of enkephalin, changes in body temperature by either cooling or heating induced epileptiform discharges that disappeared after temperature stabilization. The epileptiform episode induced by enkephalin microinjections was of longer duration at temperature below normal (29-30 degrees C). At body temperature above normal (39-40 degrees C) the epileptiform discharge was less intense and of shorter duration. In vitro testing led to parallel results: the destruction of enkephalin by the brain tissue was faster at higher temperatures. It is proposed that in conditions of hyperthermia enkephalin has a weaker activity due to acceleration of the activity of peptidases involved in its breakdown.

Animals↗
PubMed1980

Pain sensitivity and opioid activity in genetically and experimentally hypertensive rats.

Pain sensitivity was studied in renal and DOCA-salt hypertensive rats, and in two strains of rats derived from the same parental strain for their sensitivity (H) or immunity (N) to hypertension induced by DOCA-salt treatment. Experimentally hypertensive rats, and H and N rats were less sensitive to painful stimuli than their appropriate controls, as assessed in the hot-plate and paw pinch tests. Naloxone reversed this hypoalgesia in both experimentally and genetically hypertensive rats while it did not affect blood pressure in any rat-type tested. Opioid activity was measured with the radioreceptor assay in several brain regions and pituitary gland of both experimentally and genetically hypertensive rats. Experimentally hypertensive rats had a 45% higher level of opioid activity in the spinal cord compared to control. Rats of the H and N strains both exhibited higher levels of opioid activity in the spinal cord, hypothalamus and pituitary. It is suggested that control systems for blood pressure and pain sensitivity are closely associated in the rat.

Animals↗
PubMed1980

Desensitization of enucleated cells to hormones and role of cytoskeleton in control of normal hormonal response.

Prostaglandin E1 and the beta-adrenergic hormone l-isoproterenol stimulated cyclic AMP formation in both nucleated and enucleated myeloid leukemic cells that could be induced to differentiate normally to mature cells by the macrophage- and granulocyte-inducing protein MGI (MGI+D+ cells). Enucleated as well as nucleated MGI+D+ cells also desensitized to these hormones, indicating that this desensitization is an extranuclear process. Nucleated or enucleated mutant myeloid leukemic cells that are not induced to differentiate (MGI-D- cells) were not desensitized to these hormones. The antitubulin alkaloids colchicine and vinblastine, but not the antimicrofilament compound cytochalasin B, increased the maximal hormone-induced formation of cyclic AMP in nucleated MGI+D+ cells but not in the MGI-D- cells. These alkaloids also inhibited the development of desensitization to l-isoproterenol and prostaglandin E1 in enucleated MGI+D+ cells. The results indicate that in MGI+D+ cells the cytoskeletal system puts constraints on the cells' ability to respond to these hormones and that these constraints are absent in the mutant MGI-D- cells. Because MGI+D+ but not MGI-D- cells can be induced to differentiate by the macrophage- and granulocyte-inducing protein, cytoskeletal constraints, which are also found in normal myeloid cells, may be necessary for cell competence to differentiate. The results support the suggestion that membrane cytoskeletal constraints generate may control the normal response and desensitization to membrane-mediated cell inducers.

Animals↗
PubMed1980

Morphine-like peptides: their regulation in the neuroendocrine system and the effect of guanyl nucleotides and divalent ions on opiate receptor binding.

Glucocorticoids such as dexamethasone and prednisolone at physiological concentrations inhibit the synthesis, and hence the release, of endorphins by AtT/20 pituitary cells. Several other steroids, including progesterone, estradiol benzoate and testosterone, have no such effect and do not compete with dexamethasone. Incorporation of 3H-dexamethasone into nuclei of AtT/20 cells was inhibited by a much lower concentration of dexamethasone or prednisolone than that of several other steroids studied. This study indicates for the first time that glucocorticoids directly inhibit synthesis of endorphins by pituitary cells. The effect of GTP and GMP-PNP on the binding of 3H-D-ala-methionine enkephalin to rat brain opiate receptors was studied. Different brain regions showed different sensitivity to GMP-PNP. Manganese, calcium and magnesium selectively inhibited the effect of GMP-PNP but barium and strontium had no effect. The possibility that divalent cations alter the coupling of opiate receptors to internal components is suggested.

Animals↗