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D Guilloteau

Publications and source records attributed to D Guilloteau.

At least 55 records · Page 3Linked to original sources
PubMed1997

Age-related changes in phospholipid fatty acid composition and monoaminergic neurotransmission in the hippocampus of rats fed a balanced or an n-3 polyunsaturated fatty acid-deficient diet.

The influence of aging (2, 6, 12, and 24 months) on hippocampal lipid composition and neurochemical markers (endogenous noradrenaline, serotonin levels, monoamine oxidase (MOA) activities) was studied in rats fed a control or an n-3 polyunsaturated fatty acid (PUFA)-deficient diet. The n-3 PUFA deficiency reduced the 22:6 (n-3) level, compensated by the increase in 22:5 (n-6). However, the difference in 22:6 (n-3) content between control and deficient rats was less between 2 and 12 months and then became stable. There was an overall age-induced decrease in the major phospholipid classes phosphatidylethanolamine (PE), and phosphatidylcholine (PC) whereas the minor classes, phosphatidylinositol (PI), phosphatidylserine (PS), and sphingomyelin (SM), were greatly increased, regardless of diet. The n-3 PUFA deficiency induced a reduction in the PS level, concomitant with a higher level in MAO-B activity as compared to control rats at the age of 24 months. The age-related evolution of the MAO-B activity was parallel with that of noradrenaline levels in both dietary groups. The noradrenaline and serotonin levels were modified according to age but without effect of the n-3 PUFA deficiency. Results showed that the hippocampus sustained specific age-induced modifications in lipid composition and neurotransmission factors, often with a transition period between 6 and 12 months.

Aging↗
PubMed1997

N-(3-lodoprop-2E-enyl)-2beta-carbomethoxy-3beta-(3',4'-dichloro phenyl)nortropane (beta-CDIT), a tropane derivative: pharmacological characterization as a specific ligand for the dopamine transporter in the rodent brain.

N-(3-Iodoprop-2E-enyl)-2beta-carbomethoxy-3beta-(3',4'-dichl orophenyl)nortropane (beta-CDIT), a new iodinated tropane derivative, has been synthesized and radiolabeled with iodine. [125I]beta-CDIT was tested in vitro and ex vivo as a probe for the dopamine transporter site in the rat brain, and behavioral studies were performed in mice. Saturation studies in the striatum revealed that [125I]beta-CDIT bound to a single high-affinity site. The Kd value was 0.18 +/- 0.07 nM, and the corresponding Bmax value was 500 +/- 80 fmol/mg of protein. The pharmacological profile of specific [125I]beta-CDIT binding in the striatum was consistent with that of the dopamine transporter. In addition, competition studies in cerebral cortex regions with [3H]paroxetine and [3H]nisoxetine showed a very low affinity of beta-CDIT for the 5-hydroxytryptamine (Ki = 50 nM) and norepinephrine (Ki = 500 nM) transporters compared with beta-CIT (corresponding Ki values were 3 and 80 nM). In contrast, the competition of beta-CDIT with [3H]GBR 12935 in the striatal region (Ki = 29 nM) was of the same order of value as for beta-CIT (Ki = 27.5 nM). Behavioral experiments in mice showed that both beta-CDIT and beta-CIT induced stimulation of locomotor activity. Ex vivo autoradiographic studies in rats using [125I]beta-CDIT demonstrated high densities of [125I]beta-CDIT binding sites in areas known to be rich in dopaminergic innervation. Because of its high affinity and high selectivity for the dopamine transporter, [125I]beta-CDIT should be a valuable ligand for the exploration of the dopamine transporter with single-photon emission computed tomography.

Animals↗
PubMed1996

Iodolisuride and iodobenzamide, two ligands for SPECT exploration of the dopaminergic D2 receptors: a comparative study.

Iodobenzamide (IBZM) and iodolisuride (ILIS), which belong to different chemical families, are two radioligands used for SPECT imaging of dopamine D2 receptors. We have compared their cerebral biodistribution in control rats and their ability to detect quantitative modifications of D2 receptors in experimental models. IBZM and ILIS have a similar cerebral distribution in vivo in control rats and permitted the detection of upregulation of striatal dopamine D2 receptors in a model of chronic haloperidol treatment. Moreover, we observed that 1 h after injection of a saturating dose of haloperidol, IBZM uptake was 72% displaced from the striatum, while ILIS uptake was 50% displaced. In an experimental model of excitotoxic striatal lesion, the in vivo accumulation of IBZM was 30% decreased on the lesioned side, in agreement with a decrease in dopamine D2 receptor density. By contrast, the accumulation of ILIS was identical in the lesioned and in the intact striatum. From the results, it appears that IBZM and ILIS, which are both used to image dopamine D2 receptors in vivo, behave differently in pathological experimental models. The ligand for human exploration should then be chosen according to the suspected pathology.

Animals↗
PubMed1996

Iodinated PK 11195 as an ex vivo marker of neuronal injury in the lesioned rat brain.

In order to study the potentials of indirect and direct detection of neuronal damages in humans by single photon emission computerized tomography (SPECT), we compared ex vivo cerebral biodistribution of [125I]PK 11195 with that of [125I]TISCH in a rat model of unilateral striatal excitotoxic lesion. Experiments on in vitro binding with [3H]PK 11195 as a ligand for peripheral type benzodiazepine binding sites (PTBBS) and [3H]SCH 23390 as a ligand for dopamine D1 receptors were also performed to validate our experimental model. We observed a very high increase in the PTBBS and a dramatic decrease in the D1 receptors on the lesioned striatum compared to the intact side. Moreover, we showed that [125I]PK 11195 bound specifically to PTBBS in lesioned cerebral areas ex vivo 5 days after striatal infusion of quinolinic acid (600 nmoles). Increases of 192%, 168%, and 30% were obtained in the striatum, the cortex, and the hippocampus, respectively, on the lesioned side. These results showed that iodinated PK 11195 bound specifically to PTBBS ex vivo and that this binding was dramatically increased at the sites of brain lesion. This ligand could therefore be suitable to detect brain injuries in humans by SPECT, complementing the information given by ligands which image loss in a specific neuron population.

Animals↗
PubMed1996

Interaction of metaiodobenzylguanidine with cardioactive drugs: an in vitro study.

Metaiodobenzylguanidine (MIBG), an analogue of noradrenaline, is used to explore the functional integrity of sympathetic nerve endings in the human heart. Various drugs inhibit noradrenaline transport systems and may block the uptake of MIBG. As in vivo studies of the effect of these drugs on myocardial [123I]MIBG uptake are often difficult to perform, we used an in vitro human blood platelet model for this purpose. A platelet preparation from healthy volunteers was incubated with [125I]MIBG alone or different concentrations of drugs currently used in cardiology. Labetalol and propranolol inhibited [125I]MIBG uptake, whereas all other drugs tested (other beta-blockers, calcium inhibitors, digoxin and amiodarone) had no effect even at doses exceeding 50 microM. The labetalol dose inhibiting 50% of [125I]MIBG uptake was lower than the plasma concentration of this drug in treated patients, whereas the propranolol dose was higher. This in vitro study of the effect of drugs on MIBG uptake by human blood platelets is predictive of their in vivo effect on myocardial uptake of [123I]MIBG in treated patients, provided that plasma concentration is taken into account.

3-Iodobenzylguanidine↗
PubMed1996

An iodinated derivative of moclobemide as potential radioligand for brain MAO-A exploration.

In vivo evaluation of MAO-A would be of great value for the diagnosis and follow-up of therapy of depression. In order to perform this exploration by SPECT, we developed an iodinated derivative of the reversible MAO-A inhibitor, moclobemide. Ro 11-9900 was synthesized and analysed by IR, NMR and HPLC. Radioiodination was carried out by nucleophilic exchange of [125I] on the brominated precursor, and yielded [125I]-Ro 11-9900 with high specific activity. In vitro experiments on rat brain homogenates showed that Ro 11-9900 had poor inhibitory activity on MAO-A, as already described for moclobemide. By contrast, in vivo biodistribution in the rat brain showed that [125I]-Ro 11-990 accumulated in a region corresponding to the localization of locus coeruleus known for its high density of MAO-A. Moreover, preinjection of the irreversible MAO-A inhibitor clorgyline (10 mg.kg-1) prevented accumulation of radioactivity by 40 to 60% and we found that the radioactivity in the brain corresponded exclusively to [125I]-Ro 11-9900 and not to a metabolite. [125I]-Ro 11-9900 was highly accumulated in the pineal gland, both on MAO-A and on MAO-B sites. We concluded that the unmetabolized iodinated derivative of moclobemide, Ro 11-9900, preferentially labeled MAO-A in vivo in the rat brain. This compound would therefore be a potential tracer for evaluation of MAO-A by SPECT.

Animals↗
PubMed1996

Is TISCH a suitable tracer for in vivo study of modifications of the dopamine D-1 receptor?

To detect quantitative modification of dopamine D-1 receptors in vivo, we used [125I]-TISCH in an animal modelin which the striatum was unilaterally lesioned with quinolinic acid. [125I]-TISCH was injected into rats 5 days after the lesion, and the changes in receptor density obtained in vivo were compared to in vitro quantification of dopamine D-1 receptors by binding with either [125I]-TISCH or [3H]-SCH 23390 as a reference ligand. In vivo and in vitro, we obtained the same decrease (-70%) in binding of these ligands in the lesioned striatum. Using an injection of [99mTc]-DTPA to lesioned rats, we also showed the disruption of the blood-brain barrier (BBB) in the lesioned area. Thus, the equivalent decrease observed in vitro and in vivo with [125I]-TISCH confirmed that this molecule would be a valuable tool for exploration of dopamine D-1 receptors by SPECT imaging. Moreover, the fact that the breakdown of the BBB did not interfere with the receptor binding obtained in vivo may be important for future investigations in pathologies with BBB disruption, such as ischemia.

Animals↗
PubMed1996

alpha-Linolenic acid dietary deficiency alters age-related changes of dopaminergic and serotoninergic neurotransmission in the rat frontal cortex.

The effects of alpha-linolenic acid diet deficiency on rat dopaminergic and serotoninergic neurotransmission systems were investigated in the frontal cortex, striatum, and cerebellum of male rats 2,6,12, and 24 months of age. The diet deficiency induced severe decrease in the 22:6n-3 fatty acid levels in all regions and a compensatory increase in n-6 fatty acid levels. A recovery in the levels of 22:6n-3 was observed in deficient rats between 2 and 12 months of age; however, this recovery was lower in frontal cortex than in striatum and cerebellum. In the striatum and cerebellum, dopaminergic and serotoninergic receptor densities and endogenous dopamine and serotonin levels were affected by aging regardless of the diet. In contrast, a 40-75% lower level of endogenous dopamine in the frontal cortex occurred in deficient rats according to age. The deficiency also induced an 18-46% increase in serotonin 5-HT2 receptor density in the frontal cortex during aging, without variation in endogenous serotonin level, and a 10% reduction in density of dopaminergic D2 receptors. Monoamine oxidase-A and -B activities showed specific age-related variations but regardless of the diet. Our results suggest that a chronically alpha-linolenic-deficient diet specifically affects the monoaminergic systems in the frontal cortex.

Aging↗
PubMed1995

Synthesis of 4'-iodo-5-methoxy-valerophenone O-(2-aminoethyl)oxime as an agent for exploration of serotoninergic transporter.

The serotonin reuptake process is observed in the central nervous system and in cells derived from the neural crest. It would therefore be of great interest to visualize this reuptake for brain exploration and to visualize the tumors derived from these cells (Apudome). Fluvoxamine has been described as a specific uptake inhibitor for serotonin uptake and we therefore supposed that an iodinated derivative of this compound would be a suitable tracer for this purpose. We had shown by computer-assisted investigation that the trifluoromethyl group of fluvoxamine can be replaced by iodine without changing the steric hindrance of the structure. We therefore expected that this result would allow the development of a new iodinated ligand for human exploration by SPECT which would inhibit for the serotoninergic transporter. This new ligand is 4'-iodo-5-methoxyvalerophenone O-(2-aminoethyl)oxime in its E configuration. In vitro binding studies demonstrated that this iodinated ligand has a weaker affinity for the serotonin uptake sites than fluvoxamine. Steric hindrance is not sufficient to predict affinity, other structural factors such as electronic density and dipole moment must be considered to explain the biological difference between fluvoxamine and its iodinated analog.

Animals↗
PubMed1995

Iododerivative of pargyline: a potential tracer for the exploration of monoamine oxidase sites by SPECT.

Monoamine oxidases are important in the regulation of monoaminergic neurotransmission. An increase in monoamine oxidase B (MAO B) has been observed in some neurodegenerative diseases, and therefore quantification of cerebral MAO B activity by SPECT would be useful for the diagnosis and therapeutic follow-up of these disorders. We have developed an iodinated derivative of pargyline, a selective inhibitor of MAO B, in order to explore this enzyme by SPECT. Stable bromo and iodo derivatives of pargyline were synthesized and chemically characterized. The radioiodinated ligand [125I]-2-iodopargyline was obtained with high specific activity from the bromo precursor by nucleophilic exchange. Affinity and selectivity of 2-iodopargyline were tested in vitro. Biodistribution study of [125I]-2-iodopargyline was performed in rats. Radioiodinated ligand were obtained in a no-carrier-added form. 2-iodopargyline has a higher in vitro affinity for MAO B than pargyline. However, the in vitro selectivity for MAO B was better for pargyline than for 2-iodopargyline. Ex vivo autoradiographic studies and in vivo saturation studies with selective inhibitors of MAO showed that the cerebral biodistribution of [125I]-2-iodopargyline in the rat is consistent with high level binding to MAO B sites in the pineal gland and in the thalamus. In conclusion, 2-iodopargyline preferentially binds in vivo to MAO B sites with high affinity. However, its selectivity for MAO B in rats is not very high, whereas this ligand binds to a lesser extent to MAO A. It will be then of great value to evaluate the specificity of 2-iodopargyline in humans. This new ligand labeled with 123I should therefore be a suitable tool for SPECT exploration of MAO B in the human brain.

Animals↗
PubMed1995

Characterization of pharmacologically active anti-peptide antibodies directed against the first and second extracellular loops of the serotonin 5-HT1A receptor.

The immunological properties and the functional role of the first (loop I) and second (loop II) extracellular loops of the human serotonin 5-HT1A receptor were studied with three populations of anti-peptide antibodies: Ab-1 (loop I; sequence Y-Q-V-L-N-K-W-T-L-G-Q-V-T-C-D-L; residues 96-111), Ab-2 (loop II; sequence G-W-R-T-P-E-D-R-S-D-P-D-A-C-T-I-S-K-D-H-G; residues 173-193), and Ab-12 (produced against loop I but cross-reacting with loop II). Chemical modification of peptide amino acid residues revealed the importance of the polyanionic stretch near the N-terminal domain of loop II for Ab-2 antibody binding and the role of the cysteine residues in both loops for the binding of Ab-1 and Ab-12 antibodies. Antibodies Ab-2 and Ab-12 recognized only the nonglycosylated form of the receptor (42 kDa) on immunoblots with transfected HeLa cells expressing the human 5-HT1A receptor but recognized the glycosylated forms (55 and 65 kDa) of rat 5-HT1A receptor from hippocampus membranes. The Ab-1 antibodies recognized no protein band from any cell type studied. Preincubation of transfected HeLa cell membranes with Ab-2 antibodies revealed two affinity binding sites of the 5-HT1A receptor (KDH = 0.54 +/- 0.09 nM and KDL = 13.74 +/- 4.9 nM) for the agonist 8-hydroxy-2-(di-n-[3H]propylamino) tetralin ([3H]8-OH-DPAT) binding, but Ab-1 and Ab-12 revealed only one site (KD of approximately 2.5 nM). In contrast to the Ab-2 antibodies, Ab-1 and Ab-12 antibodies decreased the Bmax of the [3H]8-OH-DPAT binding to 42 and 31%, respectively. These findings suggest that there are at least two epitopes on the extracellular loops: one inducing a high-affinity state for agonist binding and the other interfering with the accessibility of the ligand binding pocket.

Amino Acid Sequence↗
PubMed1994

[Progressive supranuclear paralysis. Quantification of dopamine D2 receptors using radionuclide tomography].

Progressive supranuclear palsy (PSP) may sometimes be misdiagnosed as Parkinson's disease in its early stages, hence an early positive diagnosis of PSP based on dopamine D2 receptor density could be extremely valuable. In the present case report, the absence of dopamine D2 receptors was clearly demonstrated in the striatum using 123I-iodobenzamide (IBZM) tomoscintigraphy. This illustrates the potential use of IBZM tomoscintigraphy to identify Parkinson-like's disease presenting with decreased dopamine D2 receptor density; and hence to predict L-Dopa effectiveness. Further studies are needed to evaluate the vaue of IBZM tomoscintigraphy in the different Parkinson's like diseases.

Aged↗
PubMed1994

Radioiodinated tracers for the evaluation of dopamine receptors in the neonatal rat brain after hypoxic-ischemic injury.

In order to evaluate in vivo single-photon emission tomography (SPET) method of assessing cerebral function after hypoxic-ischemic injury in human neonates, we studied D1 and D2 dopamine receptors in a rat model. Seven-day-old rats underwent permanent unilateral common carotid ligation followed by exposure to 8% O2. Two weeks later, in brains with no visible loss of hemispheric volume, striatal dopaminergic receptors were studied, with [125I]TISCH and [125I]IBZM for the D1 and D2 dopamine receptors, respectively. Using [125I]TISCH, we observed no modifications of D1 receptors, but in contrast, ex vivo and in vitro autoradiographic experiments showed a 40% decrease in the striatal binding of [125I]IBZM on both the ipsilateral and the contralateral side to the carotid ligation. These alterations were detected with IBZM, a D2 dopamine receptor ligand usable for SPET imaging. Therefore, exploration of D2 receptors by SPET in human neonates suffering from perinatal hypoxia-ischemia may be valuable for the diagnosis and follow-up of cerebral function damages.

Animals↗
PubMed1994

Chronic dietary alpha-linolenic acid deficiency alters dopaminergic and serotoninergic neurotransmission in rats.

This study examined the effects of dietary alpha-linolenic acid [18:3(n-3)] deficiency on dopaminergic serotoninergic neurotransmission systems in 60-d-old male rats. Rats were fed semipurified diets containing either peanut oil [the (n-3)-deficient group] or peanut plus rapeseed oil (control group). We measured the densities of the serotonin-2 (5-HT2) receptors and the dopamine-2 (D2) receptors by autoradiography and membrane-binding assays in relation to the fatty acid composition and levels of endogenous monoamines in three cerebral regions: the frontal cortex, the striatum and the cerebellum. Long-term feeding of the (n-3)-deficient diet induced a significantly higher 5-HT2 receptor density in the frontal cortex compared with the control rats without any difference in the endogenous serotonin concentrations. The results also showed some modification of dopaminergic neurotransmission specifically in the frontal cortex in the rats deficient in alpha-linolenic acid, with a significantly lower density of D2 receptors and a significantly lower concentration of endogenous dopamine than in control animals. Moreover, there were lower levels of (n-3) fatty acids in all the regions studied in the deficient rats, balanced by greater levels of (n-6) fatty acids. These results suggest that chronic consumption of an alpha-linolenic acid-deficient diet could induce modifications of the neurotransmission pathways; this might induce the behavioral disturbances previously described in this fatty acid-deficient animal model.

Animals↗
PubMed1994

[Immunoassay and measurement of the biological activity of serum hLH: results obtained of a multicenter study].

The discrepancy between results obtained using different anti-hLH antibodies available on the market led us (in the context of a contract with the CNAMTS) to compare the results of hLH immunoassays (eight different reagents) with those of hLH bioassays based on the measurement of the steroidal activity of this hormone on mouse, rat or pig testicular preparations (five methodologies). Twenty-nine samples of serum or human serum pools were tested. The values resulting from these tests reveal differences linked to the nature of the antibodies or to the methodological conditions used for the testicular preparations. Some antibodies seem unable to identify some hLH forms which, however, can be detected by biological methods.

Adult↗
PubMed1993

Comparison of two radioiodinated ligands of dopamine D2 receptors in animal models: iodobenzamide and iodoethylspiperone.

Several iodinated compounds have been developed for in vivo exploration of dopamine D2 receptors by SPECT. It is of great value to understand if the same information could be obtained with different radioligands. For this purpose, we compared in vivo properties of two iodinated ligands, iodoethylspiperone (IES) and iodobenzamide (IBZM), using different pharmacological and lesioning treatments in rats. Cerebral biodistribution performed by ex vivo autoradiograms and dissection of brain areas showed that IES and IBZM bound specifically to D2 receptors since a pre-injection of haloperidol prevented accumulation of both ligands. In contrast, when haloperidol was injected after IES or IBZM, only IBZM was displaced from its binding sites. This could be explained partly by a process of dopamine-dependent internalization with IES. The response to striatal quinolinic acid infusion for lesioning post-synaptic neurons was very different for IES and IBZM. In this model a decrease in IBZM accumulation occurred, corresponding to the loss of D2 receptors located on post-synaptic neurons. In contrast, a unexpected increase in IES accumulation was observed on the lesioned side. From these results we concluded that IES and IBZM, two iodinated ligands belonging to different pharmacological families, bound specifically to dopamine D2 receptors. However they have different properties in animal models. Therefore, it appears that IBZM is a more suitable ligand than IES to detect modifications of D2 receptors by in vivo exploration.

Animals↗
PubMed1993

Receptor binding and biological effects of three 125I-iodinated estrogen derivatives in human breast cancer cells (MCF-7).

Three 125I-iodinated estrogen derivatives; 16 alpha-[125I]iodo-11 beta-methoxy-17 beta-estradiol ([125I]IME2), E-17 alpha-[125I]iodovinylestradiol ([125I]IVE2) and E-17 alpha-[125I]iodovinyl-11 beta-methoxyestradiol ([125I]MIVE2) were synthesized with high specific activities and their binding characteristics and biological effects were analyzed in vitro using the estrogen-receptor-positive human breast cancer cell line MCF-7. Direct and competitive bindings in a whole cell assay indicated that the three derivatives bound to the estrogen receptor (ER) with high affinity. The dissociation constants of the three compounds were higher than the one found for tritiated E2 suggesting that the presence of the methoxy and the vinyl groups decreased the binding affinity. The decreasing affinity order is: [3H]E2 > or = [125I]IME2 > [125I]IVE2 > [125I]MIVE2. The three unlabeled derivatives as well as E2 have been found to activate the vitellogenin promoter fused to the chloramphenicol acetyl transferase reporter gene transfected into MCF-7 cells. This assay showed that the ER is activated in the presence of the three compounds. Unlabeled IME2 produced stimulatory effects similar to those of E2 on MCF-7 growth in vitro. Unlabeled IVE2 and MIVE2 at concentrations lower than 10(-8) M enhanced MCF-7 growth but at a lower level than E2 and IME2 did. Our results clearly indicate that the three derivatives behave like estrogens and that they would be excellent candidates for imaging or monitoring ER-containing breast tumors. Because its affinity for the ER is greatest, IME2 would be the best-suited of the three as a radiotracer.

Binding, Competitive↗