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Biomedical subjects

G Fillion

Publications and source records attributed to G Fillion.

At least 91 records · Page 5Linked to original sources
PubMed1989

The effects of inorganic lead on the spontaneous and potassium-evoked release of 3H-5-HT from rat cortical synaptosome interaction with calcium.

Interaction of lead with the serotonergic system has been studied in vitro in rat brain synaptosomal fraction prepared from cortical tissue. Synaptosomes were loaded with 3H-5-HT and spontaneous and K+-evoked release of the amine was examined in the presence and the absence of calcium. It was shown that lead itself induced the release of 3H-5-HT (EC50 = 27 microM). This effect decreased (40%) in the presence of calcium without modification of the EC50. Moreover, lead markedly inhibited the K+-evoked release of 3H-5-HT observed in the presence of calcium. This effect was obtained either in the presence of lead or using synaptosomes pretreated with lead and washed. These results indicate that lead interferes with neuronal 5-HT release by mechanism(s) involving calcium.

Animals↗
PubMed1989

In vitro effect of organic and inorganic mercury on the serotonergic system.

Interactions of organic (methyl mercury) and mineral (acetate, chloride, nitrate: Hg2+) mercury salts with the serotonergic systems were studied in vitro using synaptosomal fractions prepared from rat brain cortex preloaded with [3H]5-HT. In the absence of calcium, mercury salts induced a spontaneous release of the amine corresponding to a total depletion of the synaptosomal content. EC50 for the organic and mineral forms of the ion were 66 +/- 2 microM and 107 +/- 16 microM respectively. In the presence of calcium (2.4 mM) a similar pattern of release was observed except that an additional release was induced by mineral mercury at low concentration (EC50 = 8.4 +/- 1.3 microM) which corresponded to a maximal release of 18.6 +/- 3.5% of the synaptosomal content. Therefore, the latter release appears calcium-dependent. Parallelly, the effects of mercury salts have been examined on the binding of [3H]5-HT to its high affinity 5-HT1 sites; organic and mineral mercury inhibited the binding with IC50 of 27.8 +/- 3.2 microM respectively. These results show that mercury ions interact with the serotonergic system by different mechanisms depending on their concentrations and their ionic forms.

Animals↗
PubMed1988

Postnatal development of 5-HT1 receptors: [3H]5-HT binding sites and 5-HT induced adenylate cyclase activations in rat brain cortex.

The postnatal development of the 5-HT1 receptor system was studied in young rat brain cortex from birth to adulthood (14 successive ages). The high-affinity binding of [3H]5-HT was low at birth but developed markedly between the 8th and the 15th day postnatally. The basal adenylate cyclase activity produced 50 pmoles cAMP/mg protein/min at birth and increased from the 8th to the 15th day. 5-HT could stimulate the adenylate cyclase activity in adult rat brain cortex with two different affinity constants: Km = 1 nM and Km = 0.5 microM; these low- and high-affinity constants presumably correspond to 5-HT1A and 5-HT1non-A.non-B.non-C (5-HT1D) respectively. These two activities developed parallelly from the 14-15th to the 28th day. The 8-hydroxy-2-(di-n-propylamino-tetralin) (8-OH-DPAT)-induced activity described a curve similar to the one that corresponded to 10 microM 5-HT. These results establish that 5-HT1A and 5-HT1non-A.non-B.non-C receptors mainly develop during the synaptogenesis.

Adenylyl Cyclases↗
PubMed1988

5-Hydroxytryptamine stimulates two distinct adenylate cyclase activities in rat brain: high-affinity activation is related to a 5-HT1 subtype different from 5-HT1A, 5-HT1B, and 5-HT1C.

5-HT binding sites of the 5-HT1 type are heterogeneous and appear to comprise several subtypes (5-HT1A, 5-HT1B and 5-HT1C); their physiological role is as yet unclear. The stimulation of adenylate cyclase induced by 5-HT has been investigated in membrane fractions prepared from rat brain cortex. Enzymatic activity was determined by measuring cAMP production with an HPLC technique. It was shown that 5-HT stimulates adenylate cyclase activity with 2 activation constants (Kact): one shows a high apparent affinity (Kact = 0.8 nM) and the other a lower apparent affinity (Kact = 0.30 microM). The latter activity, induced by micromolar concentrations of 5-HT, was inhibited by spiperone at concentrations that block 5-HT1A binding. 5-Methoxytryptamine, bufotenin, and LSD also had a stimulatory biphasic effect on adenylate cyclase activity, whereas trifluoromethylphenylpiperazine, 5-carboxyamidotryptamine, 8-hydroxy-(2-di-n-propylamino)tetralin, RU 24969 had a monophasic effect. Enzyme activation by drugs acting in the micromolar range was inhibited by spiperone (1 microM), suggesting a link between this activation and 5-HT1A sites. On the other hand, the high-affinity activation of the enzyme induced by 5-HT, 5-methoxytryptamine, bufotenin, LSD, and the activation induced by TFMPP were not inhibited by spiperone (1 microM), by propranolol (3 microM), or by mesulergine (0.1 microM), which selectively block 5-HT1A, 5-HT1B, and 5-HT1C sites. Inhibition was produced by dihydroergotamine, methysergide, cinanserin, and mianserin, but not by naloxone, phenoxybenzamine, and phentolamine. Therefore, these activations seem related to 5-HT1 receptors but not to 5-HT1A, 5-HT1B, or 5-HT1C sites. Accordingly, binding of [3H]5-HT to 5-HT1-like sites was examined in the presence of spiperone (1 microM) and propranolol (3 microM); in these conditions, a high-affinity site (KD = 3.4 nM) was indeed revealed. The relative potencies of a series of drugs that stimulate or inhibit the activation of the adenylate cyclase with a high affinity and their ability to inhibit this binding of [3H]5-HT showed a positive correlation, strongly suggesting a direct relation between this recognition site for 5-HT and the production of a second messenger (cAMP). Moreover, this potential receptor is shown to be heterogeneously distributed within the brain, and was localized postsynaptically at serotonergic synapses.

Adenylyl Cyclases↗
PubMed1988

Characterization and distribution of receptors for gonadotropin-releasing hormone in the rat hippocampus.

Distribution and properties of receptors for gonadotropin-releasing hormone (GnRH) were analyzed in the brain of adult male rats. Binding of the iodinated GnRH agonist Des-Gly10-(D-Ala6)-GnRH ethylamide was studied in hippocampus and anterior pituitary using three convergent approaches: quantitative autoradiography on frozen tissue, binding to fresh slices, and binding to crude membrane preparations. In all cases, binding was specific, saturable, and time, pH, and temperature dependent. Quantitative autoradiography revealed that the density of binding sites was high in the stratum oriens and stratum radiatum of the CA1-CA4 regions of Ammon's horn. The pyramidal cell layer was faintly labelled. Binding was almost undetectable in the dentate gyrus. The highest density of sites (Bmax = 11.6 +/- 1.0 fmol/mg protein) was observed in the stratum radiatum of the CA3 region. Under the same conditions the value obtained for pituitary tissues was 20.7 +/- 2.8 fmol/mg protein. Analysis of saturation curves indicated only one class of high-affinity sites for the hippocampus (CA3; Kd = 0.28 +/- 0.03 nM) and for the pituitary (Kd = 0.29 +/- 0.08 nM). Both native GnRH and GnRH antagonist were potent competitors of binding. Fresh slices and membrane preparations from whole hippocampus confirmed these autoradiographic data and yielded affinity constants of 0.28 +/- 0.01 and 0.52 +/- 0.08 nM, respectively. In addition, a very high binding density was present in the amygdaloid complex, while binding was barely detectable in the hypothalamus. These results demonstrate that high densities of specific GnRH receptors are present in areas concerned with the regulation of behavioral functions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Chronic beta-adrenergic stimulation increases in mice the sensitivity to methysergide and the number of cerebral high affinity serotonin binding sites (5-HT-1).

Reserpine administration in mice causes, among other effects an akinesia which can be reversed by the serotonin agonist-antagonist methysergide. The effect of methysergide is potentiated by clenbuterol, a beta-adrenergic agonist, which itself causes hypomotility. Potentiation is weak after a single injection of clenbuterol, but becomes much stronger after repeated administration for 12 days. This treatment also causes a 50% increase in the number of high affinity 5-HT-1 binding sites in the brain. This increase would explain the increased potency of methysergide against reserpine-induced akinesia. These results show that: a beta-adrenergic drug, clenbuterol modulates the serotoninergic system; this modulation takes its importance after chronic treatment only; this interrelation may be important in depressive illness since it is observed on a test used in the screening of antidepressant drugs.

Animals↗
PubMed1985

Multiple high affinity binding sites for 5-hydroxytryptamine: a new class of sites distinct from 5-HT1 and S2.

Two different classes of binding sites probably related to serotonergic receptors have already been reported: 5-HT1 binding sites recognize [3H]5-hydroxytryptamine with a high affinity (Kd = 3 nM) and S2 binding sites recognize [3H]spiroperidol and [3H]ketanserine. An additional population of sites has been observed in crude membrane preparations or fractions enriched with synaptosomal membranes obtained from rat brain cortex. This population was observed as a single class of sites in a synaptosomal fraction (L fraction--according to Laduron (1977)). It corresponded to a dissociation constant Kd = 13-15 nM, and Bmax = 0.80 +/- 0.15 pmol/mg protein. Displacement experiments showed that it recognized preferentially the 5-HT structure (bufotenin, 5-MeO-tryptamine). Tryptamine was a weak displacer and 5,7-dihydroxytryptamine totally inefficient. Neither 8-OH-DPAT, nor quipazine had any effect. Methiothepin, cinanserin and cyproheptadine displaced 5-HT from these sites whereas ergot derivatives did not. Contrary to 5-HT1 binding, this recently observed binding was not altered by GTP; alpha-MSH reduced the corresponding Bmax whereas Leu-enkephalin did not. The degenerative lesion of the serotonergic fibers led to a slight increase in the Bmax of the binding without altering the Kd which means that corresponding sites are not located on serotonergic fibers and might be postsynaptically located.

Animals↗
PubMed1985

Serotonin inhibits acetylcholine release from rat striatum slices: evidence for a presynaptic receptor-mediated effect.

Rat brain striatum slices were incubated with [3H]choline, perfused with a physiological buffer, and stimulated by perfusion with a K+-enriched buffer for 2 min. The tritium overflow evoked by K+ was decreased by 5-hydroxytryptamine (serotonin, 5-HT) (maximal inhibition 10(-6) M). This effect of 5-HT was mimicked by several agonists (5-methoxytryptamine, N,N-dimethyl-tryptamine, bufotenin) and blocked by serotonergic antagonists (methiothepin, methysergide, cinanserin) but not by haloperidol; methiothepin and methysergide alone slightly increased the K+-evoked overflow of tritium (3H). Inhibition of the tritium release by 5-HT was not suppressed in the presence of tetrodotoxin (TTX) (10(-6) M). These results suggest that 5-HT tonically inhibits acetylcholine (ACh) release from striatal cholinergic neurons by acting on a presynaptic receptor localized on cholinergic terminals.

Acetylcholine↗
PubMed1983

5-Hydroxytryptamine receptors in neurones and glia.

Crude membranal fractions isolated from mammalian brain tissue contain two classes of recognition sites capable of binding [3H]5-HT with high affinity constants. These classes of sits are characteristics of the postsynaptosomal membrane fraction for the higher affinity and of a glial cell membrane fraction for the lowest. They are observed with similar properties in cultured neuronal and glial cell respectively. Two 5-HT stimulated adenylate cyclases are present in crude membrane fraction; they are also separable as neuronal and glial components. These observations correspond likely to the existence of two classes of receptors for 5-HT. Their mechanisms of regulation involve presumably structural conformation changes of the recognition site coupled to various states of the activity of the receptor.

Adenylyl Cyclases↗
PubMed1982

Postnatal development of high affinity neuronal recognition sites for 3H-5-HT in rat brain.

The postnatal development of 3H-5-HT specific binding sites has been studied in rat brain. Experimental conditions allowed the characterization of the class of sites corresponding to the synaptosomal receptor for 5-HT. The related affinity constant and maximal binding were measured at various ages after birth. During the second week after birth, the serotonin receptor system developed explosively, the maximal number of sites increasing from a nonsignificant value to that observed in adult rats. Lesion of the presynaptic neurons using 5,6-DHT led to a significant increase of the number of sites.

5,6-Dihydroxytryptamine↗