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Biomedical subjects

M Hamon

Publications and source records attributed to M Hamon.

At least 469 records · Page 26Linked to original sources

Increased levels of Met-enkephalin-like material in the CSF of anaesthetized cats after tooth pulp stimulation.

Tooth pulp stimulation in halothane-anaesthetized cats induced a long lasting (greater than or equal to 3 h) increase in the levels of Met-enkephalin-like material (MELM) in the cisternal CSF. Chromatographic analyses (gel filtration, HPLC) revealed that most of the immunoreactivity was attributable to high molecular weight (mol. wt. greater than or equal to 4000) compounds; in non-stimulated cats, Met-enkephalin (largely in the form of the sulfoxide derivative) only accounted for about 10% of total MELM. In contrast, following tooth pulp stimulation, a large increase in Met-enkephalin (plus Met-Ox5-enkephalin) levels was noted so that the pentapeptide thus represented more than 50% of total MELM. No evidence was obtained for the presence of Met-enkephalin-Arg6-Phe7 in the cisternal CSF of halothane-anaesthetized cats. These data strongly suggest that the activity of enkephalinergic neurons was increased following nociceptive stimulation. This indirectly supports the possible physiological role of enkephalinergic systems in modulating nociceptive inputs.

Animals↗

Microtopography of methionine-enkephalin, dopamine and noradrenaline in the ventral mesencephalon of human control and Parkinsonian brains.

The topographical distributions of Met-enkephalin, dopamine and noradrenaline were determined in serial frontal sections of human substantia nigra (pars compacta and pars reticulata) and ventral tegmental area. Met-enkephalin was identified by Biogel and thin layer chromatography and assayed by a specific radioimmunoassay. In the substantia nigra (pars compacta and pars reticulata), the levels of Met-enkephalin increased progressively from the rostral to the caudal part of the structure. This pattern closely resembled that of dopamine levels, particularly in the pars compacta. Noradrenaline levels in the substantia nigra and those of Met-enkephalin, dopamine, and noradrenaline in the ventral tegmental area, exhibited only limited fluctuations from the anterior to the posterior part of each structure. Highly significant decreases in Met-enkephalin, dopamine and noradrenaline levels were observed in the substantia nigra and ventral tegmental area of Parkinsonian brains. This observation, together with the close topographical association of dopamine and Met-enkephalin in the substantia nigra, further supports the likely existence of important functional relationships between dopaminergic and enkephalinergic neurons in the human brain.

Aged↗

Attenuation of induced-anxiety in rats by chlordiazepoxide: role of raphe dorsalis benzodiazepine binding sites and serotoninergic neurons.

In chronically implanted awake rats, microinjections of chlordiazepoxide (5 x 10(-7) M) into the dorsal raphé significantly attenuated the inhibition of lever-pressing for food elicited by a signal of punishment. This effect is abolished by prior application of 5,7-dihydroxytryptamine into the dorsal raphé (3 weeks after the infusion of the neurotoxin, dorsal raphé tryptophan hydroxylase activity was reduced to 25% of control values). Furthermore, the disinhibitory effect of intra raphé chlordiazepoxide can be mimicked or potentiated by intra raphé dorsalis application of serotonin (10(-7) or 10(-8) M, respectively). Further evidence for a crucial interaction between benzodiazepines and serotoninergic processes are provided by in vitro experiments showing that chlordiazepoxide or diazepam (10(-5) M) are able to facilitate the K+-evoked [3H]serotonin release from rat midbrain slices. Finally, a high density of [3H]flunitrazepam binding sites was found in the dorsal (and the median) raphé nucleus, the Kd and Bmax values being not altered by prior infusion of 5,7-dihydroxytryptamine. These in vitro data suggest possible means by which intra raphé (and perhaps peripherally administered) benzodiazepines may affect the activity of serotoninergic neurons and thereby produce their effects on experimental anxiety.

5,7-Dihydroxytryptamine↗

Simultaneous measurement of beta-endorphin, lipotrophins and met-enkephalin in phaeochromocytomas.

Tissue concentrations of immunoreactive lipotrophin, beta-endorphin, and met-enkephalin were determined in 10 phaeochromocytomas, 3 of which were responsible for the ectopic ACTH syndrome. Lipotrophin and beta-endorphin immunoreactivities could be detected in all cases, whether or not Cushing's syndrome was present, and their tissue concentrations were significantly correlated (r = 0.95, P less than 0.001). Chromatographic studies showed that gamma-lipotrophin and beta-endorphin were the main peptides in the tumours. Met-enkephalin immunoreactivity was also found in all tumours examined, at much higher concentration and showing no correlation with either lipotrophin or beta-endorphin immunoreactivity. Although beta-endorphin and met-enkephalin are thought to originate from different precursor molecules, these data show that the two opioid peptides may be secreted by the same tumour. The evidence for excess secretion of opioid peptides and their pathological significance in phaeochromocytomas remain to be established.

Adolescent↗

A rapid direct radioimmunoassay for the measurement of oestrone sulphate in the milk of dairy cows and its use in pregnancy diagnosis.

A radioimmunoassay for oestrone sulphate in unextracted samples of milk has been developed. The assay was validated by comparison with a method involving hydrolysis and extraction. The direct assay was used to measure oestrone sulphate in milk samples taken at weekly intervals throughout pregnancy in a commercial dairy herd. Concentrations of oestrone sulphate increased approximately 100 days after insemination and were maintained throughout the remainder of pregnancy in the range of 1.85-3.70 nmol/l.

Animals↗

Studies on oestrogen synthesis by the preimplantation equine conceptus.

Aromatase activity measured by the incorporation of [3H]androstenedione into unconjugated and conjugated oestrogens was detectable in the equine conceptus during early pregnancy. Activity was substantially higher in yolk sac compared to allantochorion between Days 20 and 52 after ovulation. Oestrone sulphate concentrations in yolk-sac fluid measured by radioimmunoassay increased markedly to reach values of about 3 micrograms/ml at Day 36, approximately 10-fold higher than those in allantoic fluid. Extra-embryonic membranes in a 28-day conceptus all contained aromatase (chorionic girdle greater than trilaminar omphalopleure greater than bilaminar omphalopleure greater than allantochorion), implying that the enzyme complex was present in trophoblast and/or endoderm rather than mesoderm. Aromatase activity in chorionic girdle cells was low before their migration into the endometrium. Endometrial tissue contained substantial sulphotransferase and glucuronidase activity. The ability of the preimplantation equine conceptus to synthesize oestrogens was strikingly similar to that found previously in the pig; in both species the allantochorionic placenta is non-invasive.

Allantoin↗

Long lasting effects of intrauterine growth retardation of 5-HT metabolism in the brain of developing rats.

Intrauterine growth retardation (IUGR) was achieved by ligating the artery and vein supplying one uterine horn in pregnant rats on the 5th day before delivery. At birth, the weight of the whole body and of the forebrain (but not that of the brain stem of about half of the offspring) were significantly lower than those of normal controls. This deficit persisted for at least the first 3 postnatal weeks. During the immediate period following birth, the concentrations of norepinephrine, dopamine, serotonin and 5-hydroxyindoleacetic acid (5-HIAA) were significantly higher in IUGR rats than in controls. Increased levels of serotonin and 5-HIAA were still observed in the forebrain and brain stem of 15-day-old IUGR rats and were associated with parallel increases in brain and serum free tryptophan levels. These results indicate that a transient insult in the fetal life could result in long-lasting alterations in 5-HT metabolism in CNS of developing rats.

Animals↗

Kinetic characteristics of newly synthesized 3H-5-HT in the brain of control and reserpinized mice. Evidence for the heterogeneous distribution of 5-HT in serotoninergic neurons.

Following an intravenous administration of 3H-tryptophan to mice, 3H-serotonin rapidly accumulated in the brain, with a maximum around the 20th min after the injection. In mice whole monoamine oxidase activity was blocked by pargyline (75 mg/kg i.p.), reserpine pretreatment (5 mg/kg, 24 h before death) did not alter the initial accumulation of 3H-5-HT indicating that the rate of 5 HT synthesis was similar in control and reserpinized animals. When monoamine oxidase was not blocked, the accumulation of 3H-5-HT was significantly lower in reserpine-treated mice than in controls. However, the specific activity of 3H-5-HT accumulated in brain was 2-3 times higher in reserpinized (45 h) than in control mice. Since neither the specific activity of the precursor 3H-tryptophan, the reuptake process for 3H-5-HT nor the absolute synthesis rate of 5-HT was altered in the brain of reserpinized mice, it is proposed that the differences observed in the specific activity of 3H-5-HT reflected the presence of 3H-5-HT in different compartments in control and reserpinized mice. Serotonin would be distributed in a "storage" and a "functional" compartments in serotoninergic neurons under normal conditions whereas only the functional compartment would exist 18-48 h after the administration of reserpine.

Animals↗

[3H]Metergoline: a new ligand of serotonin receptors in the rat brain.

A specific binding site for [3H]metergoline characterized by a KD of 0.5-1.0 nM was detected in microsomal and synaptic plasma membranes from various areas of the adult rat brain. Experiments with 5,7-dihydroxytryptamine- and kainic acid-induced lesions indicated that this specific binding site was localized post-synaptically with respect to serotoninergic neurons. The pharmacological characteristics of [3H]metergoline binding to microsomal membranes from the whole forebrain strongly suggest that this ligand labels a class of serotonin receptors. This was particularly obvious in the hippocampus in which serotonin was about 400 times more potent than dopamine and noradrenaline for displacing bound [3H]metergoline. In the striatum, serotonin was only 10 times as potent as dopamine in inhibiting [3H]metergoline binding, suggesting that this ligand may also bind to dopamine receptors. Striking similarities between the binding sites for [3H]metergoline and [3H]serotonin were observed in the hippocampus. Thus, not only the total numbers of binding sites for these two ligands in control rats but also their respective increases following intracerebral 5,7-dihydroxytryptamine treatment were very similar. Therefore, at least in the hippocampus, [3H]metergoline might well be the appropriate ligand for studying the characteristics of the 'antagonist form' of serotonin receptors postulated by Bennett and Snyder.

5,7-Dihydroxytryptamine↗

[The possible role of neurotransmitter receptors in the mechanisms of action of antidepressants (author's transl)].

The recent discovery of atypical antidepressants like iprindole and mianserine which are devoid of any significant inhibitory effect on monoamine oxidase (MAOI) or on monoamine reuptake indicates that the antidepressant action is not necessarily associated with these two pharmacological effects. Systematic studies on the interactions of various antidepressants with the receptors for neurotransmitters reveal that the therapeutic action of these drugs is not related to the possible blockade of muscarinic, histaminergic, serotoninergic and/or alpha-adrenergic receptors in the CNS. However, chronic treatments with antidepressants (MAOIs, uptake inhibitors or atypical antidepressants) regularly induce a significant reduction in the number of beta-adrenergic and serotoninergic receptors in brain (particularly in the cerebral cortex of rats). This down regulation is associated with an hyposensitivity to NE and 5-HT agonists. These data further support the "monoamine theory" of depression: since down regulation is generally due to a long lasting overstimulation of receptors, it can be proposed that antidepressants increase NE and 5-HT neurotransmission in the CNS, notably in some depressed patients.

Animals↗