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Biomedical subjects

G Fillion

Publications and source records attributed to G Fillion.

At least 73 records · Page 4Linked to original sources
PubMed1993

Antagonism by citalopram and tianeptine of presynaptic 5-HT1B heteroreceptors inhibiting acetylcholine release.

The interactions of citalopram and tianeptine, two antidepressants having opposite effects on serotonin (5-HT) uptake, with 5-HT1B presynaptic heteroreceptors located on cholinergic terminals were investigated. In rat hippocampal synaptosomes, citalopram (0.01 or 0.1 microM) or tianeptine (0.01-10 microM) did not modify the basal or the K(+)-evoked release of [3H]acetylcholine. Only at the concentration of 100 microM did tianeptine significantly decrease (-18%) the K(+)-evoked release of [3H]acetylcholine without affecting the spontaneous outflow of radioactivity. The inhibitory effect of 7-trifluoromethyl-4-(4-1-piperazinyl)-pyrrolo[1,2-a]quinoxaline (CGS 12066B), a 5-HT1B receptor agonist, on the stimulation-induced release of [3H]acetylcholine was reduced in a concentration-dependent manner by citalopram and tianeptine. Both drugs completely reversed the inhibitory effects of CGS 12066B at concentrations that did not modify by themselves the release of [3H]acetylcholine. In contrast, tianeptine, up to a concentration of 1 microM, failed to antagonise the inhibitory effect of the muscarinic receptor agonist carbachol on K(+)-evoked [3H]acetylcholine release. Finally, the administration of tianeptine ex vivo (10 or 20 mg/kg) modified neither the depolarisation-induced release of [3H]acetylcholine nor the inhibitory effect of CGS 12066B on this presynaptic process. These findings further confirm that antidepressants interact in vitro with presynaptic 5-HT1B heteroreceptors.

Acetylcholine↗
PubMed1993

Rabies virus selectively alters 5-HT1 receptor subtypes in rat brain.

Rabies virus infection in man induces a series of clinical symptoms, some suggesting involvement of the central serotonergic system. The results of the present study show that, 5 days after rabies virus infection in rat, the total reversible high-affinity binding of [3H]5-HT in the hippocampus is not affected, suggesting that 5-HT1A binding is not altered. 5-HT1B sites identified by [125I]cyanopindolol binding are not affected in the cortex 3 and 5 days after the infection. Accordingly, the cellular inhibitory effect of trifluoromethylphenylpiperazine (TFMPP) on the [3H]acetylcholine-evoked release, presumably related to 5-HT1B receptor activity, is not modified 3 days after infection. In contrast, [3H]5-HT binding determined in the presence of drugs masking 5-HT1A, 5-HT1B and 5-HT1C receptors, is markedly (50%) reduced 3 days after the viral infection. These results suggest that 5-HT1D-like receptor subtypes may be affected specifically and at an early stage after rabies viral infection.

Acetylcholine↗
PubMed1993

Autoradiographic study of neurosteroid binding sites labelled with [35S]-TBPS in brain of different species.

Distribution of [35S]-TBPS binding sites was studied in various structures of brain in mouse and guinea pig and in cortex of monkey and in hippocampus of postmortem human brain. As it is observed for rat brain, high densities of [35S]-TBPS binding sites were found in layer IV of cortex in the four species, and in thalamus of mouse and guinea pig. Intermediate densities of binding sites were observed in superficial and deep layers of cortex in those four species and in hippocampus of mouse, guinea pig, and human. In all brain structures studied, 5 alpha 3 alpha P and picrotoxin produced a dose-dependent inhibition of [35S]-TBPS binding. No significant interregion or interspecies differences could not be detected for IC50 values of 5 alpha 3 alpha P or picrotoxin to inhibit [35S]-TBPS from its binding sites. In all regions studied, IC50 values were close to 1.5 x 10(-6) M for 5 alpha 3 alpha P and 2.3 x 10(-7) M for picrotoxin.

Animals↗
PubMed1993

Regulation of interleukin-1 receptor expression in mouse brain and pituitary by lipopolysaccharide and glucocorticoids.

Interleukin-1 (IL-1) receptors have been characterized in mouse pituitary and brain. Previous studies have demonstrated that IL-1 receptor density is high in the dentate gyrus in the hippocampus and that lipopolysaccharide (LPS) injection caused an 80% decrease in the number of hippocampal IL-1 receptors, while pituitary receptors in the anterior pituitary were unaffected. In order to investigate on the role of glucocorticoids (GC) in the control of IL-1 receptor expression in the brain and pituitary, the effect of stress, exogenous GC administration or adrenalectomy (ADX) on IL-1 receptor density was determined. Assays were achieved under basal and LPS-stimulated conditions by in situ quantitative autoradiography technique using human recombinant 125I-IL-1 alpha as a tracer. An increase of GC concentration in serum, following immobilization stress or dexamethasone (DEX) treatment (short and long term), did not modify, in the hippocampus, the density of IL-1 receptors under basal conditions or after peripheral LPS injection. On the contrary, ADX significantly decreased IL-1 receptor density in LPS-treated animals. In the anterior pituitary, a significant increase in the density of basal IL-1 receptors was observed 6 h following immobilization stress or after 7 days of DEX treatment while short-term DEX treatments are ineffective. In contrast to what was observed in the hippocampus, no changes in pituitary receptor densities were observed in ADX mice. These results indicate that hippocampal and pituitary IL-1 receptor expressions are differentially regulated by GC. Therefore, this report constitutes the first demonstration of an in vivo regulation of IL-2 receptors in the pituitary.

Adrenalectomy↗
PubMed1992

Improved brain delivery of AZT using a glycosyl phosphotriester prodrug.

The concentration of AZT in mice plasma and brain was measured using HPLC after an ingestion of 20 mg/kg of AZT or the molar equivalent of hexadecyl 2-(alpha-D-mannopyranosidyl)ethyl 3'-azido-3'-deoxy-5'-thymidinyl phosphate 3. The results demonstrated the promising qualities of the prodrug 3 which gave AZT-5'-phosphate as the main metabolite: the total concentration of AZT derivatives detected in brain presented a peak of 156 nmol/g (5 nmol/g for AZT) at 1 h; the half-life was about 24 h (1 h for AZT) with an AUC of 4366 nmol h/g as compared to 4 nmol h/g for AZT. The lipophilic properties of 3 were confirmed by its in vitro transport of inside synaptosomes. The derivative 2-(alpha-D-mannopyranosidyl)ethyl 3'-azido-3'-deoxy-5'-thymidinyl phosphate (2) provided also a good delivery of AZT to the central nervous system, with values intermediate between those of AZT and 3.

Animals↗
PubMed1992

Inhibition of [3H] gamma-aminobutyric acid release from guinea-pig hippocampal synaptosomes by serotonergic agents.

We studied the effects of (m-trifluoromethyl-phenyl)piperazine (TFMPP) and quipazine on the K(+)-evoked [3H]GABA release from guinea-pig hippocampal synaptosomes loaded with [3H]GABA.TFMPP and quipazine inhibited the K(+)-evoked release of [3H]GABA dose-dependently (IC50 = 153 and 123 microM, respectively). Serotonergic antagonists such as methiothepin (0.1, 0.3 and 1 microM), ketanserin (0.1, 0.3 and 1 microM), dihydroergotamine (0.1 microM), metergoline (0.1 and 0.3 microM), methysergide (0.3 microM), propranolol (1 microM) and yohimbine (1 microM) did not significantly alter the inhibitory effect of TFMPP on [3H]GABA release suggesting that neither 5-HT1 nor 5-HT2 receptors are involved in this process. By contrast, the effect of TFMPP was diminished by selective 5-HT3 receptor antagonist: MDL 72222 (0.3 microM), tropisetron (0.3 and 1 microM), ondansetron (0.3 microM) and metoclopramide (1 microM). Tropisetron (1 microM) and ondansetron (0.3 microM) also inhibited significantly the quipazine effect whereas methiothepin (1 microM), dihydroergotamine (0.1 microM), yohimbine (1 microM) and ketanserin (1 microM) were ineffective on the quipazine inhibition of [3H]GABA release. Our results show a serotonergic modulatory effect on the K(+)-evoked [3H]GABA release from guinea-pig hippocampal synaptosomes by receptors which are neither 5-HT1, 5-HT2 or 5-HT4. They appear to be pharmacologically related to the 5-HT3 type but different from the 5-HT3 ionic channel receptors.

Animals↗
PubMed1992

Molecular cloning of two partial serotonin 5-HT1D receptor sequences in mouse and one in guinea pig.

The G protein coupled serotonin (5-HT) receptors, with seven membrane spanning domains, form a multigene family of which several members have been cloned and sequenced. The presence of 5-HT1D binding sites to our knowledge has not yet been reported in mouse. Here we describe the cloning and sequencing by the polymerase chain reaction (PCR) method of two 5-HT1D receptor sequences of the third cytoplasmic loop in mouse, strongly suggesting the existence of two 5-HT1D receptor genes, located on chromosome 4. A homologous sequence to one of them was cloned in guinea pig.

Animals↗
PubMed1991

Receptors for interleukin-1 (alpha and beta) in mouse brain: mapping and neuronal localization in hippocampus.

Interleukin-I receptors were mapped and characterized in mouse brain by quantitative autoradiography using human recombinant [125I]interleukin-I alpha and [125I]interleukin-1 beta as ligands. Both ligands provide identical receptor mapping. In terms of specificity, interleukin-1 alpha and interleukin-1 beta were equally potent in binding competitions assays with either [125I]interleukin-1 alpha or [125I]interleukin-1 beta (EC50 11 pM). These receptors were shown to be highly concentrated in the dentate gyrus, in the choroid plexus at various levels of the brain, in the pituitary and in the meninges. They were also present at low concentrations in the cortex but undetectable in other brain structures. In the dentate gyrus, interleukin-1 receptors were localized on the granular and molecular layers (granule cells) when visualized on slides dipped in nuclear emulsion. Cellular localization of interleukin-1 receptors was assessed using selective lesion by colchicine. The complete loss of [125I]interleukin-1 binding in hippocampal areas where neurons were destroyed by colchicine demonstrates that interleukin-1 receptors are located on granule cells. Following lesion, sparse undestroyed cells, with glial cell morphology, also showed significant labelling. In conclusion, interleukin-1 receptors are located on the granule cells in the mouse dentate gyrus. These neurons may therefore be targets for neuromodulation by interleukin-1 and they may play a key role in the central effect of interleukin-1 as well as in the control of the immune response by the brain.

Animals↗
PubMed1991

Antagonism by antidepressant drugs of the inhibitory effect of trifluoromethylphenylpiperazine (TFMPP) on [3H]acetylcholine release in rat or guinea-pig hippocampal synaptosomes.

The effects of antidepressant drugs on the m-trifluoromethylphenylpiperazine (TFMPP)-induced inhibition of K(+)-evoked [3H]acetylcholine (3H-ACh) release were studied in rat or guinea-pig hippocampal synaptosomes. The serotonergic agonist TFMPP dose-dependently inhibited the K(+)-evoked release of 3H-ACh in rat hippocampus (IC50 = 53 microM). Chlorimipramine (5-500 nM), a typical tricyclic antidepressant, and minaprine (1-100 nM), an atypical antidepressant drug, partially antagonized the effect of TFMPP on 3H-ACh release in a dose-dependent manner. Other antidepressants (imipramine, citalopram, indalpine, fluoxetine, fluvoxamine, oxaprotiline, mianserine, nomifensine), at concentrations ranging from 10 to 500 nM, produced similar effects. Drugs with no antidepressant effect, such as chlorpromazine, clobazam, and cocaine (50, 100 and 500 nM), were without significant influence on the TFMPP effect. In guinea-pig hippocampal synaptosomes, minaprine (50 nM) also reduced the TFMPP-induced inhibition of 3H-ACh release, whilst clobazam (50 nM) was inactive. These results suggest that antidepressant drugs interact in vitro with heterologous serotonergic presynaptic receptors on cholinergic nerve terminals in rat and guinea-pig hippocampus.

Acetylcholine↗
PubMed1991

The inhibitory effect of trifluoromethylphenylpiperazine on [3H]acetylcholine release in guinea pig hippocampal synaptosomes is mediated by a 5-hydroxytryptamine1 receptor distinct from 1A, 1B, and 1C subtypes.

The effect of the serotonergic receptor agonist 1-(m-trifluoromethylphenyl)piperazine (TFMPP) was studied on the K(+)-evoked [3H]acetylcholine [( 3H]ACh) release from guinea pig hippocampal synaptosomes loaded with [3H]choline. TFMPP (5-1,000 microM) inhibited the evoked ACh release in a dose-dependent manner (IC50 = 81.8 microM). The inhibitory effect of TFMPP was mimicked by CGS-12066B (10, 30, and 100 microM), a 5-hydroxytryptamine1B (5-HT1B)/5-HT1D receptor agonist; 1-(m-chlorophenyl)piperazine (100 microM), a 5-HT1C/5-HT1B receptor agonist; and 5-carboxamidotryptamine (10 microM), a nonselective 5-HT1 receptor agonist. 8-Hydroxy-2-(di-n-propylamino)tetralin (10 and 100 microM), a 5-HT1A receptor agonist, and quipazine (10 and 100 microM), a 5-HT2 receptor agonist, did not have any significant effect. Serotonergic antagonists, such as dihydroergotamine (0.1 and 1 microM), metergoline (0.1 microM), methysergide (0.5 and 1 microM), or yohimbine (1 and 10 microM), blocked the TFMPP effect dose-dependently. In contrast, methiotepine (0.3 and 1 microM), propranolol (1 microM), ketanserin (0.1 microM), mesulergine (0.1 microM), ICS 205930 (0.1 and 1 microM), and spiroperidol (1 and 7 microM) did not affect the TFMPP-induced inhibition of the evoked ACh release. These data suggest that, in guinea pig hippocampus, the K(+)-evoked ACh release is modulated by a 5-HT1 receptor distinct from the 5-HT1A, 5-HT1B, and 5-HT1C subtypes.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1990

GnRH receptors in rat brain, pituitary and testis; modulation following surgical and gonadotropin-releasing hormone agonist-induced castration.

The regulation of rat gonadotropin-releasing hormone (GnRH) receptors in male rat pituitary, hippocampus and testis was studied, in vivo, under steady-state conditions during treatment with D-Trp6 GnRH (triptorelin, slow-release form, at 300 micrograms/kg/month). GnRH receptors were characterized on tissue sections by quantitative autoradiography using 125I-GnRHa as a tracer. Castrating doses of triptorelin strongly down-regulated pituitary GnRH receptors (50% of reduction after 8 h, 80% on days 1-30); in contrast, only a transient decrease (20% at 8 h) was observed in the hippocampus with a rapid return to control levels. Triptorelin induced a marked (2-fold) increase in GnRH receptors in testicular interstitial tissue during 5 days with a return to control value by day 20. Administration of a GnRH antagonist (BIM 21009, 1 mg/kg/24 h) induced a rapid reduction of pituitary and testicular receptors to undetectable levels at 24 h, while hippocampal receptors were strongly reduced only. This indicates that GnRH receptors with similar pharmacology are differently controlled in various tissues and that brain receptors are likely to be also regulated by GnRH agonists and antagonists.

Animals↗
PubMed1989

Minaprine antagonises the serotonergic inhibitory effect of trifluoromethylphenylpiperazine (TFMPP) on acetylcholine release.

The serotonin agonist, m-trifluoromethylphenylpiperazine (TFMPP), inhibited the K+-evoked release of [3H]acetylcholine ([3H]ACh) from rat hippocampal synaptosomes. The inhibitory effect of TFMPP was blocked by the non-selective 5-HT1 antagonist, methiothepin, but was not affected by ketanserin, mesulergine or spiperone. The 5-HT3 antagonist, MDL 72222, slightly reversed the inhibitory effect. The antidepressant, minaprine, did not modify the basal release of [3H]ACh but it antagonised the inhibitory effect of TFMPP on the K+-evoked release. The maximal reversal was found at 0.3 microM minaprine. These results suggest that minaprine interacts with heterologous presynaptic 5-HT1B receptors. A new approach is thus opened to the study of the mechanism of action of antidepressant drugs.

Acetylcholine↗