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Biomedical subjects

M Hamon

Publications and source records attributed to M Hamon.

At least 433 records · Page 24Linked to original sources
PubMed1984

Biochemical evidence for the 5-HT agonist properties of PAT (8-hydroxy-2-(di-n-propylamino)tetralin) in the rat brain.

In vitro investigations revealed that PAT (8-hydroxy-2-(n-dipropylamino)tetralin) interacted with postsynaptic 5-HT receptors in the rat brain: the drug stimulated 5-HT-sensitive adenylate cyclase in homogenates of colliculi from new-born rats (KAapp 8.6 microM) and inhibited the specific binding of [3H]5-HT to 5-HT1 sites. The PAT-induced inhibition of [3H]5-HT binding showed marked regional differences compatible with a preferential interaction of PAT (IC50 2 nM) with the 5-HT1A subclass. As previously seen with 5-HT agonists, the efficacy of PAT for displacing [3H]5-HT bound to hippocampal membranes was markedly increased by Mn2+ (1 mM) and reduced by GTP (0.1 mM). PAT also affected presynaptic 5-HT metabolism since it inhibited competitively (Ki 1.4 microM) [3H]5-HT uptake into cortical synaptosomes and reduced (in the presence of the 5-HT uptake inhibitor fluoxetine) the K+-evoked release of [3H]5-HT previously taken up or newly synthesized from [3H]tryptophan in cortical or striatal slices. This latter effect was prevented by 5-HT antagonists (methiothepin, metergoline) suggesting that it was mediated by the stimulation of presynaptic 5-HT autoreceptors by PAT. Like 5-HT, PAT counteracted the stimulatory effect of K+-induced depolarization on the synthesis of [3H]5-HT from [3H]tryptophan in cortical slices. It is concluded that PAT is a potent 5-HT agonist acting on both post- and presynaptic 5-HT receptors in the rat brain.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1984

Autoradiographic evidence for the heterogeneity of 5-HT1 sites in the rat brain.

The distribution of the binding sites of a new, potent agonist of serotonin (5-HT), 8-OH-N,N-dipropyl-2-aminotetralin (PAT), was studied in the rat brain with the quantitative autoradiographic technique utilizing tritium-sensitive LKB film. The localization of [3H]PAT binding sites was very similar to that of [3H]5-HT binding sites, except in some discrete regions (choroid plexus, striatum, area preoptica lateralis, subiculum, and substantia nigra), which exhibited very low levels of labeling with [3H]PAT and high levels with [3H]5-HT. These results indicate that 5-HT1 receptors are heterogeneous, and that [3H]PAT recognizes only a 5-HT1 subclass (called 5-HT1A).

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1984

Evidence against the involvement of serotonergic neurons in the anti-punishment activity of diazepam in the rat.

The effects of manipulating central serotonergic transmission were assessed on the anti-punishment effects of diazepam (2 mg/kg IP) in rats. In a paradigm involving the inhibition of pressing for food induced by the delivery of a signal previously associated with electric foot-shocks, lesioning serotonergic neurons of the dorsal raphé with the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT; 1 microgram in 0.4 microliter) neither affected behavioral inhibition in control rats nor modified the ability of diazepam to release responding. Furthermore, suppression of pressing for food induced by a fixed ratio 7 schedule of shock presentation was reduced by bilateral infusion of 5,7-DHT (2 micrograms in 0.5 microliter) into the substantia nigra, but the ability of diazepam to increase punished responding was preserved. Finally, blockade of benzodiazepine-induced decrease in serotonin release by application of the benzodiazepine receptor antagonist Ro 15-1788 (10(-5)-10(-4)M in 0.2 microliter) into the dorsal raphé did not alter the releasing effect of diazepam on suppression of pressing for food caused by a signal of punishment. At these concentrations. Ro 15-1788 was devoid of any effect on behavioral inhibition in control rats. Taken together, these results indicate that the anti-punishment activity of benzodiazepines can be dissociated from the reduction in tryptaminergic transmission produced by these drugs.

5,7-Dihydroxytryptamine↗
PubMed1984

Normal CSF levels of met-enkephalin-like material in a case of naloxone-reversible congenital insensitivity to pain.

In a case of naloxone-reversible congenital insensitivity to pain, met-enkephalin-like immunoreactivity in the CSF was in the normal range and not affected by the administration of naloxone. Chromatographic analysis of the met-enkephalin-like material revealed that it corresponded to at least two classes of molecules. A clear difference in the relative proportions of these two classes was detected in the CSF of the patient insensitive to pain when compared to controls. The possible functional significance of this alteration is discussed in relation to the well known antinociceptive action of enkephalins.

Adult↗
PubMed1984

Basic and regulatory mechanisms of in vitro release of Met-enkephalin from the dorsal zone of the rat spinal cord.

Under control conditions, superfused slices of the dorsal half of the lumbar enlargement from adult rats released Met-enkephalin-like material (MELM) that behaved as authentic Met-enkephalin under two different chromatographic procedures (Bio-gel filtration, HPLC). MELM release increased markedly on exposure of slices to batrachotoxin (0.5 microM) or to an excess of K+ (28 and 56 mM instead of 5.6 mM). The K+-evoked release was totally dependent on the presence of Ca2+ in the superfusing fluid whereas the spontaneous efflux of MELM was only partially Ca2+-dependent. Further experiments performed with tissues of polyarthritic rats indicated that the increase in their MELM levels was associated with a lower fractional rate constant of MELM release, therefore suggesting that spinal Met-enkephalin turnover might be reduced in chronically suffering animals. Examination of the possible modulation of MELM release by various neuroactive compounds present within the dorsal horn revealed that cholecystokinin (10 microM), but not its desulphated derivative, substance P-sulphoxide (10 microM), and to a lesser extent substance P, enhanced the K+-evoked MELM release. In contrast, gamma-aminobutyric acid (10 microM) and (-)-baclofen (1 microM) partially prevented the stimulatory effect of K+ on MELM release. Other compounds such as serotonin, somatostatin, and neurotensin altered neither the spontaneous nor the K+-evoked release of MELM.

Animals↗
PubMed1984

Transport of oestrone sulphate by the mammary gland in the goat.

During pregnancy in goats the concentration of endogenous oestrone sulphate in milk increased more than twofold, and that in arterial and mammary venous plasma 10- and 20-fold respectively. The concentration in milk was higher than that in arterial plasma, particularly in lactating goats during mid-gestation. This was partly related to mammary production of oestrone sulphate (or of a closely related steroid which cross-reacted in the radioimmunoassay) since in tracer infusion studies the specific activity of oestrone sulphate in milk was significantly lower than that in arterial or mammary venous plasma. It was also related to the existence of a mechanism within the gland which concentrates oestrone sulphate in milk since when infused close-arterially into the mammary gland of a non-pregnant goat with undetectable levels of the endogenous compound in the circulation, a concentration ratio of 7.4:1.0 was reached for oestrone sulphate in milk:arterial plasma. Tracer kinetic studies showed that mammary extraction of [3H]oestrone sulphate was variable (up to 41.3 +/- 30.6%, mean +/- S.E.M.). During intravenous or close-arterial infusion, radioactivity in arterial and mammary venous plasma at steady state was mainly in the form of [3H]oestrone sulphate (range, 64 +/- 10.6 to 80.2 +/- 5.9% of total radioactivity in plasma). The remainder was in the form of compounds chromatographically similar to oestradiol-17 beta-3-monosulphate, oestradiol-17 alpha-3-monosulphate and unconjugated oestrogens. The distribution of radioactivity between these different steriods was similar in arterial mammary venous plasma indicating a low level of selective mammary metabolism or extraction. The amount of labelled oestrone sulphate transferred into milk was low, and it was significantly less in pregnant (range, 0.11 +/- 0.07 to 0.27 +/- 0.16% of total infusate) than in non-pregnant animals (3.23 +/- 0.50%). Studies of the rate of transfer of [3H]oestrone sulphate from blood to milk indicated the presence of a transcellular route with peak activity in milk occurring about 110 min after the start of the infusion.

Animals↗
PubMed1984

[Possible functional significance of the simultaneous release of several putative neurotransmitters by the same neuron].

At least three criteria should be fulfilled before it can be concluded that one neurone may use more than one neurotransmitter (or neuromodulator) for synaptic transmission: Such putative neurotransmitters must be located in this particular neurone: They must be released from the neurone under physiological conditions, and: They must exert separately or together pre- and/or post-synaptic effects. Critical analysis of the literature reveals that the coexistence and corelease of neuroactive substances are rarely firmly established. However, more convincing data have been reported on the interaction at the pre- and/or post-synaptic levels between neurotransmitters possibly located in the same neuronal population. Thus, it has been shown that VIP coreleased with acetylcholine from the same parasympathetic fibres can facilitate the interaction of this neurotransmitter with muscarinic receptors on target cells. In contrast, substance P coreleased with serotonin from bulbo-spinal fibres can reduce the effect of the amine on specific presynaptic autoreceptors. The functional significance of such interactions between neurotransmitters coexisting in the same neurone seems extremely important. In particular, they might well be involved in the physiological control of hormone release from the adenohypophysis.

Animals↗
PubMed1984

[Hemofiltration].

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Acute Kidney Injury↗
PubMed1983

Parkinson's disease affects differently Met5- and Leu5-enkephalin in the human brain.

When measured in post-mortem human control brains, the ratio of Met5-enkephalin levels to those of Leu5-enkephalin varied from 1 to 13 in the 11 areas examined. In parkinsonian brains a significant reduction in the levels of both peptides was found in the pallidum and putamen whereas only Met5-enkephalin levels were decreased in the substantia nigra and ventral tegmental area. Therefore, Met5-enkephalin and Leu5-enkephalin may be located (at least partly) in different neuronal populations in the human brain.

Brain↗
PubMed1983

Biochemical and functional alterations of central GABA receptors during chronic estradiol treatment.

The characteristics of GABA and benzodiazepine receptors were examined in the hippocampus, striatum and cerebral cortex of female rats at various times (up to 9 months) after the subcutaneous implantation of an estradiol pellet (10 mg). A significant decrease in the Bmax of the high-affinity binding of [3H]muscimol to membranes from these 3 regions was detected as soon as one week after the implantation. Although the characteristics of the high-affinity binding of [3H]flunitrazepam remained unaffected during the whole treatment, the stimulatory effect of GABA (and muscimol) on this binding was significantly reduced by estrogenization. The changes in GABA receptor binding appeared functionally relevant since the elevation of striatal acetylcholine levels normally induced by the peripheral administration of muscimol (5 mg/kg) was significantly lower in estradiol-treated than in control female rats. In contrast to that observed in intact female rats, the implantation of estradiol in hypophysectomized animals did not affect the characteristics of [3H]muscimol binding to hippocampal, striatal and cortical membranes. [3H]muscimol binding was also unchanged in female rats implanted with estradiol and treated chronically with bromocriptine for 3 weeks. Since both hypophysectomy and the chronic administration of bromocriptine suppressed the hyperprolactinemia normally induced by estrogenization, the down-regulation of central GABA receptors very likely involved prolactin in intact animals implanted with 17-beta-estradiol.

Acetylcholine↗
PubMed1983

Tyrosine hydroxylase and methionine-enkephalin in the human mesencephalon. Immunocytochemical localization and relationships.

The immunocytochemical localization of tyrosine hydroxylase (TH) and methionine-enkephalin (met-enkephalin) was determined at two representative caudal and rostral levels of the human mesencephalon. Four main groups of catecholaminergic neurons were delineated, situated in the substantia nigra and the lateral, ventromedial and dorsomedial tegmentum, extending over several cytoarchitectonic divisions. They matched fairly well the dopaminergic cell groups described in monkey midbrain. TH-like immunoreactivity and neuromelanin were closely related in neurons of substantia nigra, but less so in the other groups. A widespread met-enkephalinergic innervation was observed in most areas containing catecholaminergic neurons. It followed a characteristic pattern: homogeneous and very dense in the lateral and posterior portions of substantia nigra; patchy and less dense in the other areas, the medio-ventral and periaqueductal gray being only sparsely innervated, in contrast to observations in rodents. Dopaminergic cell bodies surrounded by met-enkephalinergic varicosities were seen in most groups, particularly in the lateral substantia nigra and medioventral tegmentum. The topography of met-enkephali-like immunoreactive terminals in the substantia nigra was reminiscent of the distribution of neostriatal and pallidal afferents.

Aged↗