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Biomedical subjects

M Poulter

Publications and source records attributed to M Poulter.

At least 55 records · Page 3Linked to original sources

Neurotransmitter receptors and monoamine metabolites in the brains of patients with Alzheimer-type dementia and depression, and suicides.

In patients with Alzheimer-type dementia, in addition to the well-known losses of cholinergic neurones, there is evidence of degeneration of the noradrenergic and serotonergic innervation of the cerebral cortex. While noradrenergic and cholinergic receptors are preserved there is a loss of serotonin S1 and S2 receptors, particularly in the temporal lobe. The loss of serotonin S2 receptors may occur at an early stage of the disease and, in temporal and frontal cortex, is correlated with the loss of somatostatin immunoreactivity. In patients dying in hospital with depression, and in individuals committing suicide, there are no consistent changes in monoamine metabolites. Noradrenergic, serotonergic, and other neurotransmitter receptors were found to be unchanged, although there was a moderate decrease in imipramine binding in a small group (n = 6) of subjects with a history of depression, who had committed suicide.

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Characterisation and distribution of vasoactive intestinal polypeptide binding sites in human brain.

The binding of 125I-vasoactive intestinal polypeptide (VIP) to human brain membranes has been studied. The binding was saturable with a dissociation constant (KD) of 4.4 +/- 2.0 nM and maximum binding value (Bmax) of 8.6 +/- 6.2 fmoles/mg tissue (mean +/- SD, n = 4), and was displaced by unlabelled VIP with an IC50 of 4 nM; secretin was much less potent with an IC50 of approximately 8 microM. The regional distribution of 125I-VIP binding in human brain revealed highest binding values to be in frontal and temporal cortices with intermediate values in amygdala, caudate and cerebellum, with lowest values in hippocampus, substantia nigra and hypothalamus.

Binding Sites↗

[3H]R05-4864 and [3H]flunitrazepam binding in kainate-lesioned rat striatum and in temporal cortex of brains from patients with senile dementia of the Alzheimer type.

In agreement with other workers we report increased [3H]R05-4864 binding in kainate-lesioned rat striatum. [3H]R05-4864 binding, a possible glial marker, was also increased in temporal cortex obtained post-mortem from patients with Alzheimer's disease. [3H]Flunitrazepam binding was decreased in these brain samples, possibly indicative of neuronal cell loss. It is suggested that the poor binding characteristics of [3H]R05-4864 in human brain samples may limit its usefulness in assessing gliosis.

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The effects of cholecystokinin on dopaminergic mechanisms in rat striatum.

Intraventricular administration of cholecystokinin-octapeptide in unanesthetized rats results in a significant reduction in the number of [3H]spiperone binding sites. Striatal levels of the dopamine metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid were significantly reduced, whereas there was no significant reduction in the levels of the serotonin metabolite 5-hydroxyindoleacetic acid.

Animals↗

77Br-p-bromospiperone: a ligand for in vivo labelling of dopamine receptors.

A high striatum: cerebellum ratio of 77Br-p-bromospiperone (77Br-BrSp) was observed in rat brain following tail vein injection of the drug. Striatal 77Br-BrSp was stereospecifically displaced by the isomers of flupenthixol. After chronic haloperidol administration striatal dopamine receptor supersensitivity was demonstrated both by increased 3H-spiperone binding to striatal membranes in vitro and by increased striatal 77Br-BrSp content. These results confirm and extend previous findings and enhance interest in the use of 77Br-BrSp for the in vivo assessment of central dopamine receptors in man.

Animals↗

[3H]etorphine binding in rat striatum following lesions of the raphe nuclei.

Following 5,7-dihydroxytryptamine lesions of the rat raphe nuclei a significant reduction in striatal serotonin concentrations was observed. However, with [3H]etorphine as ligand no change in opiate receptor binding was observed in striatal membranes. Moreover, when [3H]etorphine binding was resolved into its mu- and delta + kappa-components no change in either component was observed compared with controls. It is concluded that opiate receptors are not on striatal serotonergic nerve terminals whose cell bodies are located in the raphe nuclei.

5,7-Dihydroxytryptamine↗

Hydroxy-indole-o-methyltransferase activity in human pineals: a comparison of controls and schizophrenics.

The activity of hydroxy-indole-o-methyltransferase (HIOMT) has been assayed in pineal glands from fifteen controls and twenty-three schizophrenics. There was no significant difference between the two groups in HIOMT activity and no significant effect of age, sex or neuroleptic treatment on the activity of the enzyme. A diurnal rhythm was not discernible in HIOMT activity and it is suggested that this may be the result of terminal illness. It is concluded that HIOMT activity in pineals of schizophrenics is unlikely to differ from controls.

Acetylserotonin O-Methyltransferase↗

Neurotransmitter receptors in brain in schizophrenia.

The binding of the dopamine agonist ADTN and of ligands for the serotonin, muscarinic cholinergic, GABA, and benzodiazepine receptors was studied in 18 schizophrenic and 19 control brains. By contrast with the previously reported increase in binding of the dopamine antagonist spiperone, ADTN binding was not increased, and there was no consistent change in binding of ligands for receptors of substances other than dopamine. The findings suggest that the increase in dopamine receptors (assessed by spiperone binding) in schizophrenia is related to the disease process rather than to previous neuroleptic medication, and may be limited to the type of dopamine receptors that bind butyrophenones.

Brain↗

Increased dopamine-receptor sensitivity in schizophrenia.

Dopaminergic mechanisms have been investigated in post-mortem brain specimens from nineteen patients with schizophrenia and nineteen controls. Dopamine turnover was not increased in schizophrenic patients but, as assessed by the spiroperidol-binding technique, there was a significant increase in postsynaptic receptor sensitivity. The change in the dopamine receptor occurred in nucleus accumbens, putamen, and caudate nucleus. Increased dopamine-receptor sensitivity was present in five patients who had been free of neuroleptic medication for at least 1 year before death, and therefore may be related to the disease process.

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