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A Oblin

Publications and source records attributed to A Oblin.

18 recordsLinked to original sources
PubMed1994

Complex allosteric modulation of the binding of the NMDA receptor antagonist [3H]CGP39653.

7-Chlorokynurenate, an antagonist at the glycine recognition site of the NMDA receptor complex, increases the binding of the competitive NMDA receptor antagonist [3H]CGP39653 ([3H]D,L-(E)-2-amino-4-propyl-5-phosphono-3-pentenoic acid) to well washed rat brain membranes but only in the presence of 100 microM spermine. Conversely, spermine only increases [3H]CGP39653 binding in the presence of 10 microM 7-chlorokynurenate, through a mechanism insensitive to the putative polyamine antagonists ifenprodil, arcaine or putrescine. Thus, the effects of glycine antagonists and polyamines on the binding of competitive NMDA receptor antagonists may depend on the residual glycine and polyamine content of the membrane preparation or the state of the glycine recognition site. These data further attest to the complexity of interactions between spermine and the glycine and glutamate recognition sites of the NMDA receptor.

2-Amino-5-phosphonovalerate↗
PubMed1993

Inhibition of insulin release induced by galanin in the dog is not exclusively mediated by activation of ATP-sensitive K+ channels.

Exogenous galanin (9 pmol/min during 20 min i.a.) decreased insulin levels in the plasma sampled from the pancreatic vein of the blood-perfused pancreas of dogs in which ganglionic transmission and beta-adrenoceptors had been blocked. This effect was not modified by idazoxan (1 mg/kg followed by 0.02 mg/kg/min i.v.) but was partially reduced (50%) by glibenclamide (1 mg/kg followed by 0.02 mg/kg/min i.v.). This dose of glibenclamide blocked entirely the hypoinsulinemic activity of diazoxide, an activator of pancreatic ATP-modulated K+ channels, whereas the dose of idazoxan prevented the effect of the alpha 2-adrenoceptor agonist UK-14,304. Therefore, in dogs, the decrease in insulin secretion produced by exogenous galanin is only partially mediated by activation of glibenclamide-sensitive ATP-gated K+ channels and is independent of alpha 2-adrenoceptor stimulation.

Adenosine Triphosphate↗
PubMed1992

Adrenergic and nonadrenergic cotransmitters inhibit insulin secretion during sympathetic stimulation in dogs.

Vascular and biochemical responses to pancreatic sympathetic nerve stimulation were investigated in the blood-perfused pancreas of anesthetized dogs. During sympathetic nerve stimulation, pancreatic perfusion pressure and norepinephrine release increased, whereas insulin secretion decreased. The latter effect did not occur after pretreatment with the alpha 2-adrenoceptor antagonist idazoxan. However, after beta-adrenoceptor blockade with propranolol, neither single administration of idazoxan nor the alpha 1-adrenoceptor antagonist prazosin or glibenclamide, a blocker of ATP-modulated K+ channels, affected the decrease in insulin secretion induced by sympathetic nerve stimulation. In contrast, the combination of glibenclamide with idazoxan markedly antagonised the decrease in insulin release evoked by the latter procedure. After depletion of catecholamines with syrosingopine, the stimulation-induced inhibition of insulin secretion remained unchanged even though no increases in pancreas perfusion pressure or norepinephrine release were observed. In this preparation, glibenclamide inhibited the decrease in insulin release by 50%. In animals pretreated with the neuronal blocking agent bretylium, all of the responses to sympathetic nerve stimulation were abolished. These results indicate that the inhibitory effects exerted by the sympathetic nervous system on insulin secretion are mediated not only by the classical neurotransmitter norepinephrine acting on alpha 2-adrenoceptors but also by a nonadrenergic cotransmitter that can maintain transmission under conditions of catecholamine deficiency. The postulated nonadrenergic cotransmitter(s) acts, at least partly, via the opening of ATP-modulated K+ channels blockable by glibenclamide, and its release can be prevented by the neuronal blocking agent bretylium.

Animals↗
PubMed1991

Tachykinins in the rat substantia nigra: effects of selective dopamine receptor antagonists.

The effects of sustained blockade of dopamine receptors by selective dopamine antagonists on the tachykinin (substance P and neurokinin A) content in the substantia nigra were examined. The treatment of rats for 14 days with D-1/D-2 dopamine receptor antagonist haloperidol (2 mg/kg) or selective D-2 antagonist sulpiride (100 mg/kg) produced a similar and significant decrease in nigral substance P and neurokinin A-like immunoreactivity content, about 32-36% and 27-28% of control respectively. In contrast, administration of SCH 23390 (1 mg/kg), a selective and potent D-1 dopamine receptor antagonist, failed to affect the levels of substance P and neurokinin A in the substantia nigra and did not change the sulpiride-induced reduction of the nigral tachykinin peptides. These results indicate that the D-1 dopamine receptors are not involved in the modulation of nigral substance P and neurokinin A content and suggest that the blockade of the D-2 dopamine receptor subtype exerts the same regulation of the tachykinin gene expression, in spite of the existence of three mRNAs encoding substance P and neurokinin A.

Amino Acid Sequence↗
PubMed1989

Metalloendopeptidase (EC 3.4.24.11) but not angiotensin converting enzyme is involved in the inactivation of substance P by synaptic membranes of the rat substantia nigra.

Substance P is a neuropeptide released in vivo from the substantia nigra, the principal substance P nerve terminal region in the rat brain. Its inactivation was investigated in a purified nigral synaptic membrane preparation. The membrane-bound enzyme shares many features with the endopeptidase 24-11 (EC 3.4.24.11): 1) hydrolysis of peptide bonds Gln6-Phe7, Phe7-Phe8 and Gly9-Leu10, 2) sensitivity to the inhibition by phosphoramidon and 3) relative affinity for substance P. Bestatine and captopril inhibit only the hydrolysis of the metabolites. These results suggest that substance P is inactivated in substantia nigra by endopeptidase 24-11 and that a bestatin-sensitive aminopeptidase and angiotensin converting enzyme may play a role in subsequent degradation of the substance P metabolites.

Animals↗
PubMed1988

Degradation of substance P by membrane peptidases in the rat substantia nigra: effect of selective inhibitors.

The hydrolysis of substance P by membrane peptidases prepared from the rat substantia nigra was studied in the presence of selective inhibitors. Substance P degradation by synaptic and mitochondrial membranes was completely inhibited by 1,10-phenanthroline (1 mM), a non-specific metallopeptidase inhibitor. Captopril and bestatine, selective inhibitors of angiotensin converting enzyme and aminopeptidases respectively, were without effects. However, phosphoramidon (1 microM), a putative 'enkephalinase' inhibitor, selectively inhibited substance P degradation by synaptic membranes. These results suggest that a phosphoramidon-sensitive endopeptidase may be the principal enzyme responsible for substance P degradation in substantia nigra.

Animals↗
PubMed1988

Serotonergic projections to the spinal cord but not those to the olfactory bulb also contain substance P. A combined immunocytochemical and autoradiographic study following retrograde axonal transport of [3H]serotonin labeled products.

Co-localization of substance P with serotonin in raphe projection neurons was studied by combining substance P immunocytochemistry and autoradiography following uptake and retrograde axonal transport of [3H]serotonin and/or its products from target areas. In this study, two central pathways in the rat were investigated: the serotonergic projections of the midbrain raphe to the olfactory bulb and those of the medullary raphe that innervate the thoracic spinal cord. Two hours after pargyline pretreatment, injections of 10(-4) M [3H]serotonin were made either into the olfactory bulb or into the spinal cord and respectively 24 or 60 h thereafter, rats were administered with colchicine. After a 24 h survival time, the paraformaldehyde fixed brains were investigated for substance P immunocytochemistry and then treated for light and electron microscopy autoradiography. Combining both methods, we can define on the same tissue sections at least three labeled neuronal populations: substance P immunolabeled neurons, radiolabeled neurons and doubly immuno-radiolabeled neurons. In the midbrain raphe cells as well as in the olfactory bulb nerve terminals, two kinds of labeled profiles were detected: substance P immunoreactive profiles and radiolabeled ones. The radiolabeled cell bodies of the midbrain raphe (403 counted cells) were never reactive to substance P antibodies. Moreover, they were distributed caudally to substance P stained perikarya. In contrast, in the medullary raphe, of the 336 radiolabeled cell bodies 162 were stained after substance P antibody treatment. They represent about 48% of the serotonin radiolabeled neurons projecting to the thoracic spinal cord, where a great number of varicosities were observed immunolabeled, radiolabeled and doubly immuno-radiolabeled in the dorsal horn. At the ultrastructural level, cell bodies and dendritic processes were also doubly labeled. Both labelings were observed over the cytoplasm and some organelles or perikarya. These observations provide a morphological basis to support the hypothesis that substance P can occur within some but not all serotonergic neurons and raise questions about the expression of this peptide in these systems as well as the modes of interaction of these transmitter molecules.

Animals↗
PubMed1987

Selective antagonists of dopamine receptor subtypes differentially affect substance P levels in the striatum and substantia nigra.

Repeated administration to rats of SCH 23390, a specific antagonist of the D-1 dopamine receptor, produced an increase in the substance P immunoreactivity in the striatum but not in the substantia nigra, whereas similar treatment with sulpiride, a specific D-2 dopamine receptor antagonist, reduced the nigral but not the striatal content of the peptide. When the two antagonists were given together, the SCH 23390-induced increase in striatal substance P was significantly reduced. The SCH 23390-induced increase in striatal substance P was curtailed by concomitant administration of progabide, a selective gamma-aminobutyric acid (GABA) receptor agonist. These results suggest the existence in the nigro-striatal complex of two different substance P-containing neurons which are differentially regulated by the dopamine receptor subtypes and indicate a role of GABA in the action of SCH 23390.

Animals↗
PubMed1987

Concentrations of putative neurovascular transmitters in major cerebral arteries and small pial vessels of various species.

The levels of noradrenaline, neuropeptide Y, 5-hydroxytryptamine, and substance P were measured and compared between the large arteries of the circle of Willis and the small cerebral vessels of the pia mater in the rat, rabbit, cat, and monkey. In all species, noradrenaline and neuropeptide Y concentrations were greater in the larger arteries than in small pial vessels. Noradrenaline concentrations were dramatically reduced following cervical sympathectomy, with the extent of diminution differing greatly in the various species; the effects of cervical ganglionectomy on neuropeptide Y concentrations were less pronounced. 5-Hydroxytryptamine concentrations in rats, cats, and rabbits were significantly greater in the small pial vessels, although measurable concentrations existed in the circle of Willis. In cats and monkeys, substance P was found in major arteries, but was not detectable at the level of the small pial vessels. The differences in the regional distribution of the various neurotransmitter candidates in the cerebrovascular bed may reflect their physiological significance.

Animals↗
PubMed1986

Inter- and intracellular relationship of substance P-containing neurons with serotonin and GABA in the dorsal raphe nucleus: combination of autoradiographic and immunocytochemical techniques.

Double-labeling experiments were performed at the electron microscopic level in the dorsal raphe nucleus of rat, in order to study the inter- and intracellular relationship of substance P with gamma-aminobutyric acid (GABA) and serotonin. Autoradiography for either [3H]serotonin or [3H]GABA was coupled, on the same tissue section, with peroxidase-antiperoxidase immunocytochemistry for substance P in colchicine-treated animals. Intercellular relationships were represented by synaptic contacts made by [3H]serotonin-labeled terminals on substance P-containing somata and dendrites, and by substance P-containing terminals on [3H]GABA-labeled cells. Intracellular relationships were suggested by the occurrence of the peptide within [3H]serotonin-containing and [3H]GABA-containing cell bodies and fibers. Doubly labeled varicosities of the two kinds were also observed in the supraependymal plexus adjacent to the dorsal raphe nucleus. The results demonstrated that, in addition to reciprocal synaptic interactions made by substance P with serotonin and GABA, the dorsal raphe nucleus is the site of intracellular relationships between the peptide and either the amine or the amino acid.

Animals↗
PubMed1985

Progabide reverses the nigral substance P reduction induced by chronic impairment of dopaminergic transmission.

Repeated treatment with haloperidol or lesion of nigrostriatal dopaminergic neurons with 6-hydroxydopamine produced a reduction in substance P immunoreactivity in the rat substantia nigra. This reduction was reversed by the repeated administration of progabide, a selective GABA receptor agonist. As GABA inhibits substance P release, these results suggest that the reduction in nigral substance P levels was due to an increased liberation of the peptide probably related to deficient GABAergic function induced by impairment of striatal dopaminergic transmission.

Animals↗
PubMed1985

Influence of GABA mimetics and lithium on biochemical manifestations of striatal dopamine target cell hypersensitivity.

The potential mechanisms whereby GABA mimetics and the antimanic agent lithium stabilize dopaminergic transmission are discussed. Evidence is presented that GABA mimetics, and in particular progabide, affect dopamine-mediated events in the basal ganglia on at least three levels. First, they reduce dopamine neuron activity in both the basal and the activated states. Secondly, on a long-term basis, they antagonize the proliferation of striatal dopamine receptors subsequent to chronic neuroleptic treatment. Thirdly, they modulate the expression of dopamine receptor activation by acting distally to the dopaminergic synapse. Lithium and GABA mimetics have the last two properties in common. These effects may represent the biochemical basis for the therapeutic action of GABA mimetics in iatrogenic dyskinesias. Moreover, the similarity between the biochemical effects of GABA mimetics and lithium suggest that the former drugs may have a therapeutic potential in mania.

Animals↗
PubMed1984

Involvement of the D-2 dopamine receptor in the neuroleptic-induced decrease in nigral substance P.

Repeated treatment with, but not single administration of drugs which impair dopaminergic transmission produced a consistent reduction in substance P immunoreactivity in the rat substantia nigra. This effect appears to be related to the D-2 dopamine receptor function as the blockade of this receptor subtype by selective antagonists produced effects qualitatively similar to those produced by drugs lacking selectivity for different subclasses of dopamine receptors.

Animals↗
PubMed1983

Influence of lithium on biochemical manifestations of striatal dopamine target cell supersensitivity induced by prolonged haloperidol treatment.

The effects of prolonged treatment with dietary lithium and/or haloperidol (infused by means of osmotic minipumps) on biochemical parameters indicative of striatal dopamine target cell supersensitivity have been investigated in the rat. When given concomitantly with haloperidol, lithium failed to prevent the fall of striatal dopamine metabolites observed 2 days following withdrawal and the tolerance to the elevation of dopamine metabolites in response to challenge with the neuroleptic during withdrawal. Prolonged treatment with lithium also failed to modify the changes in nigral dihydroxyphenylacetic acid levels and in striatal acetylcholine levels which occur under chronic neuroleptic treatment. Chronic dietary lithium alone consistently elevated substance P levels in substantia nigra. The usual decrease in nigral levels of the peptide that occurs in response to chronic treatment with haloperidol was prevented in animals treated concomitantly with lithium. These data suggest that the mechanism whereby lithium stabilizes dopaminergic supersensitivity does not seem to involve an action of the compound on the neuronal mechanisms regulating the activity of the nigro-striatal dopaminergic system or on striatal cholinergic neurons but may be related to the restoration of normal striato-nigral substance P ergic transmission.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1983

Solid-phase radioimmunoassay for substance P.

The solid-phase immunoassay for quantification of substance P has been developed. The assay is based on the repartition of anti-substance P antibodies between the insoluble phase-immobilized substance P and the free peptide. The immobilized substance P-antibody complex is then quantified with 125I-protein A. The method allowed detection of 10 pg of substance P. The values of substance P concentration obtained by the present method in different regions of the rat brain were comparable to those obtained by standard radioimmunoassay with 125I-tyr-8-substance P as tracer. The described solid-phase radioimmunoassay is a simple, sensitive, and reliable technique for quantification of substance P-like immunoreactivity in biological samples.

Animals↗
PubMed1978

Biological effects of chrysotile after SO2 sorption. II. Effects on alveolar macrophages and red blood cells.

An experimental study has been carried out using different biological and biochemical in vivo and in vitro tests for assessing the toxicity of natural UICC (A) chrysotile and SO2-sorbed UICC (A) chrysotile and for detecting a possible synergistic effect. For in vivo studies, rabbits received an intratracheal injection of chrysotile fibers suspended in physiological saline (PS). The control group received only PS; all animals were sacrificed after 68 hr. The alveolar free cells were harvested by pulmonary lavage. The results have shown that chrysotile induces a decrease in the free cell population but there was no significant difference in the number of viable cells or in the nature of cells harvested between the two chrysotile groups. Enzymatic activities of the alveolar macrophages from animals injected with SO2-sorbed chrysotile showed a significant increase of the enzymes LDH and acid phosphatases. The LDH increase could be related to the affinity of the enzyme regarding some chemical forms of SO2. In vitro studies using alveolar macrophages harvested by pulmonary lavage have shown no differences between the two chrysotile groups when cell viability and enzyme release were studied. The toxic effect was due to chrysotile fibers (decrease of 38% in cell viability and increase in cellular enzyme release when compared with control). When rabbit red blood cells were used, both natural and SO2 chrysotile fibers showed the same hemolytic activity. The failure to detect high differences between the two chrysotile groups may be related to the chemical form of sorbed SO2.

Acetylglucosaminidase↗
PubMed1978

Biological effects of chrysolite after SO2 sorption. iii. effects on the biochemical components of alveolar washing.

The short-term effects of chrysotile asbestos before and after SO2 sorption are studied in the rabbit after intratracheal injection of low doses of these pollutants. Chrysotile, as well as SO2-chrysotile, induces an increase in the unsaturated fatty acid content of lung surfactant, which is similar to that observed in the respiratory distress syndrome of the newborn, and an increase in the protein level of pulmonary washings which may be explained by an increase of the permeability of the blood-air barrier. These soluble proteins can interact with the surfacant and thus decrease its tensio-active properites.

Animals↗