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R Cortés

Publications and source records attributed to R Cortés.

At least 73 records · Page 4Linked to original sources
PubMed1988

Benzodiazepine receptor sites in the human brain: autoradiographic mapping.

Receptor autoradiography was used to localize and quantify the distribution of benzodiazepine receptor sites in human post mortem materials using [3H]flunitrazepam. The distribution and density of these sites was analysed in the brains of 21 patients dying without reported neurological disease. The distribution of benzodiazepine receptors in the human brain was found to be comparable from case to case although differences in the density occurred among the brains examined. No influence of the post mortem delay, age, gender or pre mortem drug treatment on the distribution and densities was observed in our series. The highest densities of benzodiazepine receptors in human brain were localized in cortical and hippocampal areas, nucleus accumbens, amygdala and mammillary bodies. Intermediate densities were found in the basal ganglia and thalamic and hypothalamic nuclei. [3H]Flunitrazepam binding was low in the brainstem nuclei and very low in white matter. The triazolopyridazine Cl 218872, reported to differentiate between type I and type II benzodiazepine receptor sites, exhibited regional differences in affinity when used to block [3H]flunitrazepam binding. Benzodiazepine receptors in the cerebellar cortex were more sensitive to this compound than those in the dentate gyrus of the hippocampus and the tuberal nuclei of the hypothalamus. An enrichment in the concentration of type I benzodiazepine receptor Cl 218872-sensitive sites was observed in motor areas as compared to structures of the limbic system. The addition of GABA to the incubation medium resulted in an increase of [3H]flunitrazepam binding, suggesting the coupling of these sites to a GABAA receptor. The increase in binding was directly proportional to the density of benzodiazepine receptors but unrelated to the density of high-affinity GABAA sites. The distribution of benzodiazepine receptor sites in the human brain compares well with that previously described in the rat brain. The high densities of receptors localized in the limbic system and in the cortical areas suggest that the effects of benzodiazepines are mediated through an interaction with the sites we have visualized in these anatomical structures. Our results provide a detailed map of the distribution of benzodiazepine receptors and a basis for the understanding of pharmacological effects of these drugs in humans and for future studies of modifications of these receptors in neurological and neuropsychiatric conditions in humans.

Aged↗
PubMed1988

Autoradiography of antidepressant binding sites in the human brain: localization using [3H]imipramine and [3H]paroxetine.

[3H]Imipramine and [3H]paroxetine were used to label sites associated with serotonin uptake mechanisms in post-mortem brain tissue from control subjects. The anatomical localization of these sites was examined by autoradiography and densities measured by microdensitometry. We found [3H]imipramine binding to increase with age in the cortex and amygdala, but to be independent of gender and post-mortem delay. Preliminary results indicate that the binding of both [3H]imipramine and [3H]paroxetine is diminished in the brain of patients treated with imipramine. The distribution of [3H]imipramine and [3H]paroxetine high-affinity binding sites was very similar, and correlated well with the distribution of serotonergic presynaptic markers in the brain. The highest densities of binding sites were found in the raphé nuclei and the midline thalamic nuclei. Other structures presenting high levels of binding were the substantia nigra, nucleus interpeduncularis, locus coeruleus, nucleus nervi hypoglossi, nucleus nervi facialis, mammillary bodies and other parts of the hypothalamus. In contrast, regions such as the neocortex, hippocampus, amygdala and cerebellum showed low densities of [3H]imipramine and [3H]paroxetine binding sites. This distribution seems to indicate that the ascending serotonergic pathways are the main site of action of antidepressants.

Aged↗
PubMed1988

Antiserum raised against residues 159-168 of the guanine nucleotide-binding protein Gi3-alpha reacts with ependymal cells and some neurons in the rat brain containing cholecystokinin- or cholecystokinin- and tyrosine 3-hydroxylase-like immunoreactivities.

Antibodies raised against a synthetic deca-peptide corresponding to a specific sequence of Gi3-alpha protein (an inhibitory guanine nucleotide-binding protein) were used to analyze Gi3-alpha-like immunoreactivity in brain sections from colchicine-treated rats by indirect immunofluorescence histochemistry. Gi3-alpha-peptide-positive cell bodies were found in the ventral tegmental area and substantia nigra, and these cells were also cholecystokinin (CCK)- and tyrosine 3-hydroxylase-positive. Gi3-alpha-peptide staining was observed in perikarya in the hippocampus and in fibers in the nucleus accumbens, tuberculum olfactorium, bed nucleus of stria terminalis, and a spino-thalamic tract, where it coexisted with CCK-like immunoreactivity as well. No coexistence with CCK occurred in Gi3-alpha-peptide-positive ependymal cells outlining the aqueduct and ventricles. Preadsorption of Gi3-alpha antibodies with CCK-8 or CCK-33 did not alter Gi3-alpha-peptide staining. The occurrence of Gi3-alpha-peptide-like immunoreactivity in CCK-containing neurons may indicate the presence of Gi3-alpha protein and in CCK/dopamine neurons may indicate an association of this Gi protein with dopamine autoreceptors.

Animals↗
PubMed1988

Receptors in human brain diseases: a use for receptor autoradiography in neuropathology.

The application of the technique of in vitro receptor autoradiography to the study of neurotransmitter receptor alterations associated with human brain diseases is reviewed. Focus is made on receptor alterations in Parkinson's disease and Senile Dementia. Different types of modifications have been found. The most important are 1) receptor changes related to a specific neuronal loss; 2) receptor regulation associated with modifications of presynaptic input; 3) receptor changes which cannot directly be related to neuronal loss or presynaptic changes. The possible value as a diagnostic tool and the utility of receptor autoradiography in neuropathology is discussed.

Autoradiography↗
PubMed1987

Autoradiographic localization of muscarinic cholinergic receptors in visual areas of cat brain: variations in sensitivity of N-[3H]methylscopolamine binding sites to carbachol and pirenzepine.

The distribution of muscarinic acetylcholine receptors (MChRs) was studied in visual areas of cat brain using in vitro quantitative autoradiography with 1 nM N-[3H]methylscopolamine ([3H]NMS) as a radioligand. The highest density of [3H]NMS binding was observed in lamina A of the lateral geniculate nucleus (LGN) and in layer II/III of the visual cortex. The lowest binding was seen in the stratum griseum intermediale of the superior colliculus (SC). The comparison of inhibition of [3H]NMS binding by 100 microM carbachol and 300 nM pirenzepine showed that the SC and LGN contain predominantly M2 sites. M1 sites constitute the main population of MChRs in the cortical areas studied.

Animals↗
PubMed1987

alpha 1-Adrenoceptors in the mammalian brain: similar pharmacology but different distribution in rodents and primates.

We have used membrane binding assays and in vitro autoradiographic techniques to study the characteristics and distribution of alpha 1-adrenoceptors in the brain of the rat, mouse, guinea pig, cat, pig, monkey and man. 125I-BE 2254 was used as ligand. The binding characteristics of alpha 1-adrenoceptors in the cortex of the rat and pig and the human cortex and hippocampus were fully comparable as shown by the binding profile of a series of alpha 1-adrenergic compounds. Differences were, however, seen in the densities of sites in human and rat hippocampus. Contrasting with the similarities seen in the pharmacological characteristics of alpha 1-adrenoceptors in the brain of several mammals, autoradiographic results showed dramatic differences in the regional distribution of brain alpha 1-adrenoceptors. While the thalamus and cortex were rich in alpha 1-sites in all the species investigated, differences in the nuclear and laminar distributions were seen between rodents and primates. One of the most important differences was the high density of alpha 1-adrenoceptors in the human and monkey hippocampus, mainly in the CA3, CA4 and dentate gyrus, while in all the other species investigated, the hippocampal formation was poor in these sites. These results suggest that, while alpha 1-adrenoceptors appear to be similar in their pharmacology, their distribution differs among these 6 mammals. Thus, different patterns of central activity can be expected from alpha 1-adrenergic drugs in the rodent and in the primate and man.

Animals↗
PubMed1987

Distinct topographical localisation of two somatostatin receptor subpopulations in the human cortex.

The use of two different radioligands, [125I]Leu8, D-Tryp22,Tyr25-somatostatin-28 and the stable somatostatin octapeptide analog [125I]204-090, D-Phe-Cys[125I]Tyr-D-Trp-Lys-Thr-Cys-Thr(ol), allowed to differentiate between two somatostatin receptor subpopulations in the human cortex. In homogenates, octapeptide somatostatin analogs displaced only part of the somatostatin-28 radioligand with high affinity. Autoradiography showed that the receptor subpopulation labelled with [125I]204-090, which we named SS1, was preferentially localized in layers V and VI, whereas the subpopulation having low affinity for somatostatin octapeptides (named SS2), measured with somatostatin-28 radioligand, was concentrated in the superficial cortical layers (I-IV) and particularly enriched in parts of lamina IV.

Aged↗
PubMed1987

Quantitative light microscopic autoradiographic localization of cholinergic muscarinic receptors in the human brain: forebrain.

The distribution of muscarinic cholinergic receptors in the human forebrain and cerebellum was studied in detail by quantitative autoradiography using N-[3H]methylscopolamine as a ligand. Only postmortem tissue from patients free of neurological diseases was used in this study. The highest densities of muscarinic cholinergic receptors were found in the striatum, olfactory tubercle and tuberal nuclei of the hypothalamus. Intermediate to high densities were observed in the amygdala, hippocampal formation and cerebral cortex. In the thalamus muscarinic cholinergic receptors were heterogeneously distributed, with densities ranging from very low to intermediate or high. N-[3H]Methylscopolamine binding was low in the hypothalamus, globus pallidus and basal forebrain nuclei, and very low in the cerebellum and white matter tracts. The localization of the putative muscarinic cholinergic receptors subtypes M1 and M2 was analysed in parallel using carbachol and pirenzepine at a single concentration to partially inhibit N-[3H]methylscopolamine binding. Mixed populations of both subtypes were found in all regions. M1 sites were largely predominant in the basal ganglia, amygdala and hippocampus, and constituted the majority of muscarinic cholinergic receptors in the cerebral cortex. M2 sites were preferentially localized in the diencephalon, basal forebrain and cerebellum. In some areas such as the striatum and substantia innominata there was a tendency to lower densities of muscarinic cholinergic receptors with increasing age. In general, we observed a slight decrease in M2 sites in elderly cases. Muscarinic cholinergic receptor concentrations seemed to be reduced following longer postmortem periods. The distribution of acetylcholinesterase was also studied using histochemical methods, and compared with the localization of muscarinic cholinergic receptors and other cholinergic markers. The correlation between the presence of muscarinic cholinergic receptors and the involvement of cholinergic mechanisms in the function of specific brain areas is discussed. Their implication in neurological diseases is also reviewed.

Aging↗
PubMed1987

Beta-adrenergic binding sites in fetal rat central nervous system and pineal gland: their relation to other receptor sites.

Regional development of beta-adrenergic binding sites in the rat fetal central nervous system and pineal gland were studied in relation to the ontogeny of different drug and neurotransmitter binding sites. 3H-dihydroalprenolol labels the olfactory bulb very early in fetal life. A comparatively early development of binding sites is also seen for benzodiazepines during late gestation. 3H-serotonin, 3H-muscimol, 3H-GABA and 3H-(N)-methylscopolamine additionally label the olfactory bulb, revealing quite different patterns. Around gestational day 16, beta-adrenergic sites were found in the neocortex, then in choroid plexus and in the pineal gland. Besides beta-adrenergic, only 3H-flunitrazepam binding sites are detectable in the fetal eye, the latter with a more restricted regional distribution. In the fetal pineal, beta-adrenergic, muscarinic cholinergic and serotonergic binding sites appear at different times in gestation. In the neocortex a variety of binding site patterns develop. Two more general types can be distinguished: appearance along with caudorostral maturation of the brain and appearance within distinct brain regions, possibly related to local differentiation processes. The simultaneous onset of various binding sites in distinct areas of the fetal brain might result in higher sensitivity of individual brain areas to drugs.

Animals↗
PubMed1987

Receptor plasticity in the human brain: some autoradiographic studies.

Receptor modifications in human postmortem material were studied by quantitative autoradiography. Alterations of several neurotransmitter receptors in neurodegenerative diseases such as senile dementia and Huntington's chorea, in lesions of specific brain pathways, like the visual pathway or after drug treatments, were examined. In all these situations alterions of the density or localization of receptors were seen using autoradiography. The results suggest that several mechanisms of receptor adaptation operate in the human brain. These mechanisms include: compensatory changes in receptor density as a consequence of cell loss, in some cases preceding the neuropathological changes; differential alterations in receptors depending on their location in a given pathway, for example in the visual pathway or selective homologous or heterologous modification of receptors after drug treatment.

Antidepressive Agents↗
PubMed1986

Muscarinic cholinergic receptor subtypes in the rat brain. I. Quantitative autoradiographic studies.

The binding characteristics of N[3H]methylscopolamine ([3H]NMS) to slide-mounted tissue sections were studied using quantitative autoradiography. Binding of [3H]NMS was saturable, reversible and of high affinity (Kd = 0.26 nM). The inhibition of [3H]NMS binding produced by several muscarinic agonists and antagonists was analyzed in 29 discrete brain regions by constructing complete displacement curves. Comparison of IC50 values obtained both biochemically and by autoradiography demonstrated a very close agreement, supporting the validity of the autoradiographic approach. The competition curves for the agonists carbachol, oxotremorine and 2-ethyl-8-methyl-2,8-diazaspiro-[4,5]-decan-1,3-dion-h ydrobromide (RS 86) fitted to a two-site model, with comparable affinity values from region to region, although different proportions of high- and low-affinity sites were seen in the different areas studied. The distribution of high- and low-affinity sites was similar for the three agonists. Atropine showed monophasic curves presenting similar affinities in all regions studied. In contrast, pirenzepine differentiated between high- and low-affinity sites which showed a distribution opposite to that observed for the agonists. Gallamine, a ligand for a putative regulatory site in the muscarinic receptor, inhibited [3H]NMS binding in a biphasic manner. The calculated IC50 values for the gallamine high- and low-affinity sites did not vary from region to region and the distribution of these sites correlated well with that observed for the agonists. High-affinity pirenzepine sites (also called M1 sites) were localized mainly in forebrain areas, such as striatum, hippocampus and cortex, and their regional distribution correlated with that of the low-affinity sites for the agonists and gallamine. On the other hand, low-affinity sites for pirenzepine (named M2 sites) were mainly found in the brainstem and parts of the thalamus. A good correlation was found between pirenzepine low-affinity sites and agonist and gallamine high-affinity sites. The significance of these findings is discussed in relation to the known and possible effects of selective M1 and M2 centrally acting agents.

Animals↗
PubMed1986

Muscarinic cholinergic receptor subtypes in the human brain. II. Quantitative autoradiographic studies.

The distribution and characteristics of M1 and M2 muscarinic cholinergic receptors as defined by their affinity for the antagonist pirenzepine were studied in the human brain using in vitro quantitative autoradiographic techniques. The binding of N-[3H]methylscopolamine ([3H]NMS) to cortical and striatal microtome tissue sections was saturable and presented a Kd of 0.25 nM. The sensitivity of [3H]NMS-binding sites to 100 microM carbachol and 300 nM pirenzepine was analyzed in 30 brain areas. In selected brain regions, complete competition curves using carbachol, pirenzepine and atropine were analyzed. Finally, the regional distribution of M1 sites was studied using [3H]pirenzepine ([3H]PZ) as ligand. The binding of [3H]NMS to striatum, hippocampus and amygdala was very sensitive to pirenzepine but not to carbachol. The opposite situation was found in thalamus, hypothalamus, substantia innominata, pons and medulla, while intermediate sensitivity to both displacers was observed in different layers of the cortex and in the claustrum. Competition experiments showed that [3H]NMS binding was displaced with the same affinity by atropine in all the regions studied, while the IC50 of carbachol varied from 5 microM in the nucleus facialis to 830 microM in the caudate. Pirenzepine IC50 values for [3H]NMS sites varied from 66 nM to 1 microM. Results using [3H]PZ further confirm this pattern of distribution, with high densities of binding observed in the striatum, hippocampus and amygdala and very low in thalamic and brainstem areas. These results show that the putative M1 and M2 muscarinic receptor subtypes present a differential anatomical distribution in the human brain. This differential distribution is comparable to that observed in the rat brain. Some basal ganglia and limbic areas are enriched in M1 sites, while thalamus, brainstem, medulla and also the hypothalamus and substantia innominata contain predominantly receptors of the M2 type. The cerebral cortex is an example of a region containing a mixed population of M1 and M2 sites. These results provide an anatomical description of the distribution of subtypes of the muscarinic receptor in the human brain, which can be related to the known pharmacological effects of muscarinic agents in brain function.

Aged↗
PubMed1986

The distribution of glycine receptors in the human brain. A light microscopic autoradiographic study using [3H]strychnine.

Glycine receptors were localized autoradiographically in postmortem human brain material using [3H]strychnine as a ligand. Slide mounted tissue sections were labeled in vitro by incubation with [3H]strychnine and autoradiograms obtained using [3H]Ultrofilm. Receptor densities were quantified by computer assisted microdensitometry. No specific binding of [3H]strychnine was observed in any of the forebrain areas studied. Low densities were seen in the midbrain except for dorsal and lateral parts of the periaqueductal grey matter and the oculomotor nuclei. In pons, medulla oblongata and upper cervical cord high densities of [3H]strychnine binding sites were associated with some nuclei including the motor and sensory trigeminal nuclei, the facial and the hypoglossal nuclei. The highest densities of grains were associated with the substantia gelatinosa of the trigeminal nucleus in the medulla oblongata. A peculiar spotty distribution of [3H]strychnine binding sites were found in the gracilis and cuneatus nuclei. The distribution of glycine receptors in the human brain is comparable to that seen in the rat brain, although densities are much higher in the rat. The distribution of glycine receptors in the human brain provides an anatomical substrate for the understanding of the effects of drugs acting in these receptors, particularly strychnine.

Accessory Nerve↗
PubMed1985

Quantitative autoradiographic mapping of serotonin receptors in the rat brain. II. Serotonin-2 receptors.

The distribution of serotonin-2 (5-HT2) receptors in the rat brain was studied by light microscopic quantitative autoradiography. Receptors were labeled with four ligands: [3H]ketanserin, [3H]mesulergine, [3H]LSD and [3H]spiperone, which are reported to show high affinity for 5-HT2 receptors. Co-incubation with increasing concentrations of several well-known 5-HT2-selective drugs, such as pirenperone, cinanserin and ketanserin, resulted in an inhibition of the binding of the four 3H-labeled ligands to the same areas. However, all of them recognized, in addition to 5-HT2 sites, other populations of binding sites. Receptor densities were quantified by microdensitometry with the aid of a computer-assisted image-analysis system. Our results reveal a heterogeneous distribution of 5-HT2 receptor densities in the rat brain. Very high concentrations were localized in the claustrum, olfactory tubercle and layer IV of the neocortex. The anterior olfactory nucleus, piriform cortex and layer I of neocortex were also rich in 5-HT2 receptors. Intermediate concentrations of receptors were found in caudate putamen, nucleus accumbens, layer V of neocortex, ventral dentate gyrus and mammillary bodies. Areas containing only low concentrations of receptors included the thalamus, hippocampus, brainstem, medulla, cerebellum and spinal cord. The specificity of the different ligands used is discussed in terms of the other populations of sites recognized by them. The distribution of 5-HT2 receptors here reported is discussed in correlation with (a) the known distribution of serotoninergic terminals, (b) the specific anatomical systems and (c) the central effects reported to be mediated by 5-HT2-selective drugs.

Animals↗
PubMed1985

Thyrotropin-releasing hormone receptor binding sites: autoradiographic distribution in the rat and guinea pig brain.

Thyrotropin-releasing hormone (TRH) binding sites were labeled in vitro in mounted brain tissue sections from rat and guinea pig brains with [3H]methyl TRH and localized autoradiographically using 3H-sensitive film. Regional densities of TRH binding sites were measured by computer-assisted microdensitometry. The distribution of sites in both species was highly heterogeneous. In both guinea pig and rat brains, the highest densities of binding sites were seen in the amygdaloid nuclei and the perirhinal cortex. In contrast, in other brain areas, a clear difference between the distribution of sites in rat and guinea pig was found. The temporal cortex, pontine nuclei, and interpeduncular nucleus, which contained high densities of binding in the guinea pig, were scarcely labeled in the rat. The accessory olfactory bulb and the septohippocampal area presented in the rat higher concentrations of binding sites than in the guinea pig. Other brain areas showing intermediate to low densities in both species were accumbens nucleus, bed nucleus of the stria terminalis, dentate gyrus, facial and hypoglossal nuclei, and gelatinosus subnucleus of the trigeminal nerve, among others. The anterior pituitary also presented low to intermediate concentrations of receptors. The distribution of TRH sites here described does not completely correlate with that of endogenous TRH, but is in good agreement with previous biochemical data. The results are discussed in correlation to the physiological effects that appear to be mediated by TRH.

Animals↗
PubMed1984

Distribution of alpha 2-adrenergic receptors in the human brainstem: an autoradiographic study using [3H]p-aminoclonidine.

The distribution of alpha 2-adrenergic receptors in the human brainstem and some forebrain areas was examined by means of an in vitro autoradiographic technique using [3H]p-aminoclonidine as a ligand. High densities of alpha 2-adrenergic receptors were observed in the dorsal motor nucleus of the Xth nerve, the nucleus of the solitary tract, the locus coeruleus and the substantia grisea centralis. Other brainstem areas presenting significant densities of alpha 2-adrenergic receptors were the substantia gelantinosa of the Vth nerve, the nucleus cuneiformis, the superficial gray layer of the superior colliculus, the cortical mantle of the inferior colliculus and the inferior olivary nuclei. Of the forebrain areas studied, the highest density was seen in the primary visual cortex. The distribution observed presents some significant differences with that previously described for the rat. The localization of alpha 2-adrenergic receptors in the human brain correlates well with the distribution of noradrenergic neurons in the human brainstem and suggests sites of action of alpha 2-adrenergic drugs in the human brain.

Adrenergic alpha-Agonists↗