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Biomedical subjects

M Hamon

Publications and source records attributed to M Hamon.

At least 505 records · Page 28Linked to original sources
PubMed1979

Ontogenesis of tryptophan transport in the rat brain.

During the first three postnatal weeks, the levels of tryptophan in the brain are exceptionally high, 2--4 times those found in adult rats. This is related to two main peculiarities concerning tryptophan transport in young animals: 1. the lack of tryptophan binding onto serum albumin which makes its diffusion from plasma to tissues easier for the early life period; 2. the greater capacity of synaptosomes from neonates to accumulate tryptophan. Experiments consisting of electrolytic lesioning of the midbrain raphé or 5, 7-dihydroxytryptamine treatment clearly demonstrate that the uptake or tryptophan during postnatal development is not more active in serotoninergic than in other types of nerve terminals. In adult rats, changing the concentration of tryptophan induces parallel modifications in the rate of 5-HT synthesis in the brain since the rate limiting enzyme, tryptophan hydroxylase, is not saturated by its substrate. In contrast, neither tryptophan loading, nor parachlorophenylalanine administration (resulting in a marked decrease in brain tryptophan levels) alters the rate of 5-HT synthesis in the CNS of neonates, indicating that tryptophan hydroxylase is saturated during the early life period. These results are discussed in relation to the possible non-transmitter role of 5-HT during brain growth.

Aging↗
PubMed1979

In vitro and in vivo disposition of 3H-methiothepin in brain tissues. Relationship to the effects of acute treatment with methiothepin on central serotoninergic receptors.

A single treatment with a large dose of methiothepin (20 mg/kg, i.p.) induced, as early as the 2nd day after injection, a significant increase (+20--35%) in the number of specific binding sites for 3H-5-HT in forebrain areas, particularly the hippocampus. Experiments with 3H-methiothepin indicated that the drug remained firmly bound to brain membranes thus maintaining a local concentration high enough to effectively block 5-HT receptors for 10--12 h after its peripheral administration. Accordingly, it can be concluded that the occupancy of central 5-HT receptor sites by methiothepin for several hours was sufficient to induce a supersensitivity phenomenon within the two following days. Although 3H-methiothepin was a useful marker for analyzing the disposition and the kinetics of the 5-HT antagonist in brain tissues, it could not be used as a specific ligand of 5-HT receptors in brain since under in vitro as well as in vivo conditions most of 3H-methiothepin bound to non-specific sites, especially to the lipid component of the membranes.

Adenylyl Cyclases↗
PubMed1978

Paradoxical decrease of brain 5-HT turnover by metergoline, a central 5-HT receptor blocker.

Since metergoline (1-methyl-8-beta-carbobenzyloxy-aminomethyl-10-alpha-ergoline) is a potent 5-HT antagonist in peripheral organs, its possible blocking effects on 5-HT receptors in the rat brain were investigated. In vitro, metergoline inhibited both the specific high affinity binding of 3-H-5-HT onto synaptosomal membranes (IC 50 = 18 nM) and the stimulating effect of 10 micron 5-HT on the adenylate cyclase activity in colliculi homogenates from newborn rats (IC 50 = 12 micron. In vivo, the administration of metergoline (10 mg/kg i.p., 60 min before death) resulted in a significant decrease in the 3-H-5-HT binding capacity of synaptosomal membranes from the forebrain of adult rats. Taken together, these data clearly indicated that metergoline is a potent blocker of some serotoninergic receptors in the rat brain. Surprisingly, the changes in 5-HT turnover occurring in the brainstem and in the forebrain 1 h after metergoline (2-10 mg/kg) treatment were similar to those normally induced by a central 5-HT agonist: both the rate of 5-HT utilisation and that of 5-HT synthesis were significantly decreased. These changes were in contrast to the acceleration of 5-HT turnover induced by the administration of another potent central 5-HT antagonist, methiothepin. These results are discussed in relation to the possible existence of several types of serotoninergic receptors in the rat brain. It is possible that the positive feedback regulation of 5-HT turnover is triggered by the blockade of serotoninergic receptors sensitive to methiothepin, but not to metergoline.

Adenylyl Cyclases↗
PubMed1978

Characteristics of the activation by dithiothreitol and Fe(2+) of tryptophan hydroxylase from the rat brain.

The preincubation of tryptophan hydroxylase extracted from various areas of the central nervous system of the rat with 30 mM dithiothreitol and 50 muM ferrous ammonium sulfate under nitrogen atmosphere resulted in a persistent increase of its activity. Studies on the enzyme characteristics indicated that this activation was associated with a doubling in its Vmax and a shift (from 7.6 to 7.2) of the optimal pH for its activity. In contrast, the molecular weight and the apparent affinities of tryptophan hydroxylase for its pterin cofactor and for tryptophan were not significantly altered by the preincubation with dithiothreitol and ferrous ammonium sulfate. Since this treatment did not prevent the stimulatory effects of various compounds (phosphatidylserine, ATP and MG(2+), Ca(2+)) on tryptophan hydroxylase activity, this might be a good procedure to activate this enzyme with only minor changes in its regulatory properties.

Animals↗
PubMed1978

Release of endogenous serotonin from two identified serotonin-containing neurones and the physiological role of serotonin re-uptake.

1. The amounts of endogenous serotonin (5-HT) released into the medium by the cerebro-buccal ganglionic ring of Aplysia californica incubated in artificial sea water (ASW) were measured. The rate of spontaneous 5-HT release varied between 0.4 and 1.2 p-mole per hour, which is less than 1% of the total 5-HT present in this preparation.2. Direct stimulation of the ordinarily silent 5-HT-containing giant cerebral neurones resulted in a 80-100% increase of the 5-HT released, but only when the 5-HT uptake was blocked by chlorimipramine (1-10 muM).3. High K(+) media (50 mM) also caused a significant increase in the amount of 5-HT released from the preparation provided that chlorimipramine (1-10 muM) was present in the incubation fluid.4. Co(2+) ions (10-30 mM) added to the incubating medium blocked the spontaneous leak of endogenous 5-HT as well as the release, in the presence of chlorimipramine, evoked either by stimulation of the 5-HT-giant cerebral neurones or high K(+)-media.5. In the presence of chlorimipramine or desmethylimipramine, the duration and/or the amplitude of the excitatory or the inhibitory synaptic potentials evoked in the buccal neurones by the stimulation of the 5-HT giant cerebral neurones were markedly enhanced.6. These results strongly support the idea that 5-HT is the synaptic transmitter released at the excitatory and inhibitory junctions established by the 5-HT giant cerebral neurones in the ipsilateral buccal ganglia. In addition, they underline the role of amine re-uptake in the physiological inactivation of 5-HT as a transmitter.

Action Potentials↗