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Biomedical subjects

R Kerwin

Publications and source records attributed to R Kerwin.

At least 55 records · Page 3Linked to original sources
PubMed1992

Distribution of CCK binding sites in the human hippocampal formation and their alteration in schizophrenia: a post-mortem autoradiographic study.

The distribution of cholecystokinin binding sites has been visualized and quantified by quantitative autoradiography in the human hippocampus from post-mortem brains of 11 controls and 11 schizophrenics. CCK receptors were localized to subiculum and parahippocampal gyrus. In the cortical areas there was a particularly dense lamination of receptors. In the schizophrenic material a similar overall pattern was seen, but there were significant losses of receptors in CA1 subiculum and cortex. These findings confirm the distribution of CCK receptors in the retrohippocampal areas in man and also provide further support for earlier homogenate studies which have also shown a loss of CCK binding sites in schizophrenia. This effect was localized primarily to parahippocampal gyrus suggesting that CCK plays some role in the genesis of developmental abnormalities in this region.

Adult↗
PubMed1990

Quantitative autoradiographic analysis of glutamate binding sites in the hippocampal formation in normal and schizophrenic brain post mortem.

Using quantitative autoradiography, the anatomical distribution of the binding sites (kainate, N-methyl-D-aspartate and quisqualate) for the excitatory neurotransmitter glutamate has been established in the hippocampal formation from control and schizophrenic brains, post mortem. There is a loss of the kainate subtype particularly in schizophrenic hippocampi mainly from the CA4/CA3 mossy fibre termination zone of the cornu ammonis (CA4 and CA3; control and schizophrenic left hippocampus, respectively, 54.2 and 66.6 pmol/g; 18.3 and 17.9 pmol/g), as well as bilateral losses in the dentate gyrus (left 14.2 pmol/g and right 28.0 pmol/g; left 9.5 pmol/g and right 7.9 pmol/g, control and schizophrenic, respectively) and parahippocampal gyrus (left 50.8 pmol/g and right 41.7 pmol/g, left 27.7 pmol/g and right 25.3 pmol/g, control and schizophrenic, respectively). There is complete preservation of N-methy-D-aspartate sites in schizophrenic hippocampi, and a marginally significant loss of the quisqualate binding site in CA4/CA3 regions (left 249 fmol/g and right 306 fmol/g, left 157 fmol/g and right 148 fmol/g, control and schizophrenic, respectively). These findings reflect the possible importance of glutamate in the pathophysiology of schizophrenia and represent novel targets for therapeutic manipulation in schizophrenia.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1987

Coronary artery infusion of neuropeptide Y in patients with angina pectoris.

Neuropeptide Y was infused into a coronary artery of 6 patients with typical angina but no significant coronary stenosis. 3 patients had transient myocardial ischaemia, shown by typical pain and electrocardiographic change, at doses of 0.2 pmol/kg per min in 2 patients and 1.0 pmol/kg per min in 1 patient. The arteriographic appearances suggested constriction of small vessels rather than constriction of epicardial coronary arteries. The ischaemia was completely reversed by intracoronary administration of isosorbide dinitrate with no adverse sequelae. This is the first demonstration of myocardial ischaemia in man induced by a peptide neurotransmitter.

Adult↗
PubMed1984

Functional increase in striatal dopaminergic activity following continuous long-term treatment with trifluoperazine.

Acute administration of trifluoperazine (2-10 mg/kg i.p.) caused a dose-dependent increase in potassium (K+)-evoked release of [3H]acetylcholine from striatal slices, but was without effect on K+-evoked release of [3H]glutamate. K+-evoked [3H]acetylcholine release was not different in striatal tissue from rats receiving 1 year's continuous administration of trifluoperazine (4.5-5.1 mg/kg/day) compared to age-matched control animals. However, K+-evoked striatal [3H]glutamate release was decreased in tissue from chronically trifluoperazine-treated animals compared to age-matched controls. The reversal of the acute action of trifluoperazine on striatal [3H]acetylcholine and the decrease of [3H]glutamate release on chronic administration is consistent with adaptive changes in striatal dopamine transmission during long-term neuroleptic treatment.

Acetylcholine↗
PubMed1983

Long-term adaptive changes in striatal dopamine function in response to chronic neuroleptic intake in rats.

Chronic neuroleptic drug administration to rats reverses initial dopamine receptor blockade so that animals exhibit striatal dopamine receptor supersensitivity. This effect may be of functional significance in the whole animal for it is accompanied by increased striatal acetylcholine content and by reversal of the acute increase in striatal acetylcholine release. Continuous drug intake may increase the number of striatal 3H-spiperone binding sites while decreasing the number of 3H-N, n-propylnorapomorphine binding sites. While D-2 adenylate cyclase independent dopamine receptor binding sites increase in number, no change occurs in the number of D-1 sites labelled by 3H-piflutixol despite increased adenylate cyclase activity. Haloperidol and sulpiride differentially alter striatal 3H-acetylcholine and 3H-glutamate release in a manner suggesting selective changes in dopamine receptors lying on striatal cell bodies and on the terminals of corticostriate glutamate terminals. In summary, neuroleptic drugs induce a series of adaptive changes on chronic administration consistent with the development of functional striatal dopamine receptor supersensitivity.

Acetylcholine↗
PubMed1980

GABA inhibition of 3H-glycine release from slices of rat substantia nigra in vitro.

3H-Glycine was released by 50 mM K+ in a calcium-dependent manner from rat substantia nigra slices. This release was abolished by GABA (0.1-1 mM) and muscimol (0.1 mM). Taurine and beta-alanine were without effect on evoked 3H-glycine release. The effect of GABA (0.5 mM) was reversed picrotoxin (50 micro M). These results support the hypothesis that GABA receptors may be present on glycinergic interneurones in the substantia nigra.

Animals↗
PubMed1978

Baclofen (beta-p-chlorophenyl-gamma-aminobutyric acid) enhances [3H]gamma-aminobutyric acid (3H-GABA) release from rat globus pallidus in vitro.

The rat globus pallidus has been investigated as a possible model in which to study pre-synaptic GABA mechanisms in vitro. (+/-)-Baclofen (300 micrometer-1 mM) significantly enhanced the release of radioactivity from superfused slices of rat globus pallidus prelabelled with 3H-GABA in vitro. This releasing action was specific to the (+)-isomer of baclofen: neither the (-)-isomer nor another neuronal depressant dl-alpha-epsilon-diaminopimelic acid had any significant effect. The releasing effect of baclofen appeared unrelated to the phenethylamine moiety of its structure as neither beta-phenethylamine nor dopamine evoked release of 3H-GABA from pallidal slices. Baclofen increased the efflux of radioactivity from pallidal slices prelabelled with either [3H]-beta-alanine or [3H]diaminobutyric acid in vitro. The use of specific glial and neuronal GABA uptake blocking compounds (beta-alanine and (+/-)-cis-1,3-amino-cyclohexanecarboxylic acid) did not permit resolution of the elements from which baclofen was evoking [3H]GABA release. Baclofen also inhibited uptake of [3H]GABA into pallidal slices with an IC50 value of 6 x 10(-4) m. The GABA-like properties of baclofen may be related to the (+)-isomer while non-specific neuronal depressant actions are an effect of the (-)-isomer. The potential of the (+)-isomer as an antipsychotic agent while (-)-baclofen remains the effective antispastic drug free from unwanted side-effects, is discussed.

Alanine↗
PubMed1978

Dopamine receptors in the central thermoregulatory pathways of the rat.

1. Intrahypothalamic injection of either dopamine (10 microgram) or apomorphine (10 microgram) in a dose volume of 1 microliter. caused an almost immediate rise in tail skin temperature and a concomitant fall in core temperature in the conscious rat maintained at an ambient temperature of 17 +/- 1 degrees C. 2. The location of the dopamine-sensitive site was defined more accurately by reducing the dose volume to 0.5 microliter. and injecting dopamine at different points throughout the preoptic and anterior hypothalamic region. 3. The largest mean fall in core temperature (1.13 +/- 0.22 degrees C) was obtained after injection into the preoptic region. Injections with their perimeters more than 0.4 mm rostral or caudal to this site were ineffective. 4. Rats placed 0.65 m below a 250 W infra-red lamp responded to the imposed heat load by vasodilation of the tail skin blood vessels, indicated by an increased tail skin temperature. 5. Bilateral, but not unilateral, injection of either pimozide (0.5 microgram) or haloperidol (2.5 microgram) into the preoptic region significantly reduced the increase in tail skin temperature so that the rats were less able to withstand the imposed heat load. 6. Three serial sections (0.5 mm thick) were prepared from the preoptic anterior hypothalamic region of the rat brain, one anterior, one posterior and one corresponding to the dopamine-sensitive site. 7. Tissue from the middle slice increased its rate of synthesis of 3,5-cyclic AMP in response to addition of dopamine 20 or 100 micron to the incubation medium. The posterior slice was inactive, but the anterior slice had similar activity to the middle slice. 8. The effect of dopamine on the middle slice was specifically blocked by haloperidol (0.1 micron), whereas the effects on the anterior slice were partially blocked by both haloperidol (0.1 micron) and propranolol (0.1 micron). 9. These results indicate that there is within a well defined area of the preoptic region a population of dopamine receptors, which play a part in the transmission of information from warm sensors to heat loss effectors.

Animals↗