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Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Subtypes of the angiotensin II (Ang II) type-1 (AT1) receptor are probably involved in distinct actions of the peptide, since their distribution in peripheral organs and regulation of their gene expression are different. We investigated the distribution of AT1A and AT1B receptor subtype mRNAs in the rat forebrain and pituitary using sensitive cRNA probes for in situ hybridization. High level of AT1A receptor mRNA expression is observed in the subfornical organ (SFO) and in the anterior hypothalamus, particularly the periventricular tissue surrounding the anterior portion of the 3rd ventricle (AV3V), which contains the organum vasculosum of the lamina terminalis (OVLT), the median preoptic nucleus and the preoptic periventricular nucleus as well as in the hypothalamic periventricular nucleus and in the parvocellular part of the paraventricular nucleus (PVN). Moderate to strong AT1A labeling was found in the anterior olfactory nucleus, the piriform cortex and the nucleus of the lateral olfactory tract. Very low AT1B receptor mRNA expression was found in the SFO and the PVN. In contrast, strong AT1B receptor mRNA expression coincided with low AT1A receptor mRNA expression in the anterior pituitary. Labeling was cytoplasmic at the light microscopic level. We thus suggest that the AT1A receptor is responsible for the central actions of Ang II in the rat forebrain whereas direct actions of Ang II on the anterior pituitary are mediated by the AT1B receptor subtype.
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PMID:The angiotensin receptor subtype AT1A predominates in rat forebrain areas involved in blood pressure, body fluid homeostasis and neuroendocrine control. 760 44

Recently developed antisera selective for angiotensin Type 2 (AT2) receptors were used to localize AT2 receptors in rat brain by immunohistochemistry. While the results from these experiments were largely consistent with previous autoradiographic and radioligand binding analyses of AT2 receptor populations in brain, there were also some notable differences in the distribution of immunoreactivity. More specifically, in agreement with previous studies, AT2 antisera detected apparent receptor populations in the locus coeruleus and the bed nucleus of the accessory olfactory tract, whereas AT2 receptor-immunoreactivity in the cerebellum was primarily associated with the Purkinje cell layer and the deep cerebellar nuclei rather than the molecular layer as has been previously reported in autoradiographic studies. Other regions with prominent immune-staining included all subfields of the hippocampus, which had been previously reported to contain exclusively AT1 receptors. Limbic structures such as the amygdala, thalamic areas such as the rhomboid thalamic nucleus, the paraventricular thalamic nucleus, hypothalamic areas such as the paraventricular hypothalamic nucleus, and the supraoptic nucleus also exhibited prominent AT2-immunoreactivity. In the paraventricular hypothalamic nucleus, AT2 receptor staining appeared to be associated primarily with the magnocellular neurons. In all regions examined, AT2 receptor immunoreactivity was associated with the cytoplasm and cell membrane and was not localized within the nucleus. Collectively, these results confirm and extend the neuroanatomical resolution of previous autoradiographic studies as well as identify new AT2 receptor populations in rat brain.
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PMID:Immunohistochemical mapping of angiotensin type 2 (AT2) receptors in rat brain. 785 90

Rat acetyltransferases (ATs) can acetylate the endogenous arylalkylamines tryptamine, 5-hydroxytryptamine (serotonin), and 5-methoxytryptamine, the immediate precursor of melatonin. The same enzymes also acetylate and activate exogenous, carcinogenic arylamines, thereby being immediately responsible for the generation of DNA adducts. Localization of AT transcripts in the pineal gland and in specific cells of the intestine, cerebral cortex, pituitary, and lung identifies cells that may be important to the neurotransmitter and hormonal roles of the tryptamine derivatives. Transcript localization i liver, mammary gland, Zymbal gland, kidney, forestomach, and bladder, as well as intestine and lung, identifies cells that may be at increased carcinogenic risk because they can convert N-hydroxylated arylamines to genotoxic metabolites. Highly specific expression is also observed in the reproductive organs of both the male and female, including the testes, epididymis, uterus, ovary, and fallopian tube. In addition to these diverse organs, which are consistent with possible roles of the enzyme in carcinogen metabolism, neurotransmission, or hormonal regulation, specific cells of the cornea, cilliary process of the eye, olfactory process, adrenal gland, exorbital lacrimal gland, and skin also exhibit highly specific expression of AT mRNAs for which one can only speculate as to their function. In virtually every case, the extent of labeling suggested that AT1 was expressed at levels that were orders of magnitude higher than those of AT2. Qualitative differences in the sites of mRNA of these two enzymes were seen only in the olfactory process, in which AT1 was expressed in both respiratory and olfactory epithelia as well as Bowman's cells, and AT2 was detected only in the latter cells. The available data support the conclusion that the ATs are likely to be involved both in the metabolic activation of exogenous carcinogenic amines as well as the metabolism of endogenous arylalkylamines that play important hormonal and neurotransmitter roles.
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PMID:Histological localization of messenger RNAs for rat acetyltransferases that acetylate serotonin and genotoxic arylamines. 860 96

To analyze cell-specific brain gene expression, we have developed a PCR-based subtractive hybridization cloning method utilizing trace starting material, allowing isolation of novel genes expressed under specific conditions. Our previous studies indicated that local substantia nigra (SN) type 1 astrocytes elaborate an array of trophic molecules which support the survival of SN dopaminergic neurons. Therefore, the current study focused on astrocyte gene expression utilizing a type 1 astrocyte-enriched cDNA library. We report initial characterization of a novel cDNA, designated AT1-46, that is preferentially expressed in the olfactory-limbic system of the adult rat brain. Although AT1-46 is expressed widely in the periphery, it is regulated both developmentally and in a cell-specific fashion in the brain. Structurally, AT1-46 is predicted to encode a highly alpha-helical molecule with several domains of potential coiled coil formation, and exhibits a 28% amino acid sequence identity with the intermediate filament-associated protein, trichohyalin.
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PMID:The identification of a novel cDNA preferentially expressed in the olfactory-limbic system of the adult rat. 879 3

Angiotensin II receptors are highly localized in adult gerbil brain. Apparent receptor number is high in subfornical organ, vascular organ of the lamina terminalis, nucleus of the solitary tract, hippocampus, and in the anterior pituitary gland. In the hippocampus, binding is localized to the stratum oriens, radiatum, the lacunar molecular layers of the CA1 subfield, and the molecular layer of the gyrus dentatus, with a medial to lateral and anterior to posterior gradient in receptor expression. Binding is absent from the pyramidal layer of the CA1 subfield and from the granular cell layer of the gyrus dentatus, areas rich in angiotensin IV binding. Characterization in the hippocampus revealed the presence of a high affinity receptor, sensitive to incubation with the guanine nucleotide GTP gamma S, and displaced by angiotensin II = angiotensin III < Sar1-Ile8-angiotensin II, but not by angiotensin IV or other angiotensin fragments, the AT1 receptor antagonist losartan, or the AT2 ligands CGP 42112 or PD 123177. In other brain areas, binding was equally insensitive to displacement by AT1 or AT2 ligands, with the exception of binding in the olfactory bulb, which was totally displaced by CGP 42112 and PD 123177, but not by losartan. In the gerbil, most of the brain and pituitary angiotensin II receptors are different from the AT1, AT2 and AT4 subtypes, and should be considered 'atypical' until further characterization.
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PMID:Expression of a novel angiotensin II receptor subtype in gerbil brain. 882 48

The discovery of a novel, non-AT1, non-AT2 binding site for angiotensin II (Ang II) in the brain adds a new dimension to the brain angiotensin system. The distribution of the non-AT1, non-AT2 binding site in the rat brain was determined using radioligand-binding assays and in vitro receptor autoradiography. There is a marked rostral to caudal gradient of the density of this binding site from the olfactory bulbs to the cervical spinal cord, with a consistent binding affinity, K(d) approximately 1-3 nM. Binding is widespread throughout the brain, however, areas of very intense binding are present in a large number of brain regions. The olfactory nerve layer of the olfactory bulb has the highest binding site density. Very high binding site density is also seen in the cerebral cortex with highest binding density in pyriform, insular and entorhinal cortex. Very high binding occurs in brain regions associated with dopaminergic reward (nucleus accumbens, ventral tegmental area) and motor (substantia nigra, caudate/putamen) systems. Very high to high binding also occurs in brain regions associated with the development of Alzheimer's disease (nucleus basalis of Meynert, substantia innominata). Very high to high binding is also seen in brain regions associated with cardiovascular regulation (subfornical organ, median, medial and anteroventral preoptic nucleus, paraventricular nucleus of the hypothalamus, solitary tract nucleus), areas that harbor high densities of the AT1 Ang II receptor subtype. High non-AT1, non-AT2 binding site density is present in brain regions containing high levels of the AT2 Ang II receptor subtype (amygdala, several thalamic nuclei, superior colliculus). Very high binding is also present in the choroid plexus, peri-third ventricular ependyma, and the subcommissural organ. The widespread, yet discrete distribution of high levels of this binding site suggests that it could function as a component of the blood-brain barrier, as a highly specific angiotensinase, or as a receptor for Ang II that mediates known and novel functions of this peptide, or that it serves as a clearance receptor for Ang II.
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PMID:Distribution of the non-AT1, non-AT2 angiotensin-binding site in the rat brain: preliminary characterization. 1856 84

Breast cancer susceptibility gene 1 (BRCA1) is a breast and ovarian cancer tumor suppressor whose loss leads to DNA damage and defective centrosome functions. Despite its tumor suppression functions, BRCA1 is most highly expressed in the embryonic neuroepithelium when the neural progenitors are highly proliferative. To determine its functional significance, we deleted BRCA1 in the developing brain using a neural progenitor-specific driver. The phenotype is characterized by severe agenesis of multiple laminated cerebral structures affecting most notably the neocortex, hippocampus, cerebellum, and olfactory bulbs. Major phenotypes are caused by excess apoptosis, as these could be significantly suppressed by the concomitant deletion of p53. Certain phenotypes attributable to centrosomal and cell polarity functions could not be rescued by p53 deletion. A double KO with the DNA damage sensor kinase ATM was able to rescue BRCA1 loss to a greater extent than p53. Our results suggest distinct apoptotic and centrosomal functions of BRCA1 in neural progenitors, with important implications to understand the sensitivity of the embryonic brain to DNA damage, as well as the developmental regulation of brain size.
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PMID:Role of BRCA1 in brain development. 2463 35

The molecular pathogenesis of ataxia-telangiectasia (A-T) is not yet fully understood, and a versatile cellular model is required for in vitro studies. The occurrence of continuous neurogenesis and easy access make the multipotent adult stem cells from the olfactory mucosa within the nasal cavity a potential cellular model. We describe an efficient method to establish neuron-like cells from olfactory mucosa biopsies derived from A-T patients for the purpose of studying the cellular and molecular aspects of this debilitating disease.
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PMID:A Patient-Specific Stem Cell Model to Investigate the Neurological Phenotype Observed in Ataxia-Telangiectasia. 2847 34

The renin-angiotensin system (RAS), and particularly its angiotensin type-2 receptors (AT2), have been classically involved in processes of cell proliferation and maturation during development. However, the potential role of RAS in adult neurogenesis in the ventricular-subventricular zone (V-SVZ) and its aging-related alterations have not been investigated. In the present study, we analyzed the role of major RAS receptors on neurogenesis in the V-SVZ of adult mice and rats. In mice, we showed that the increase in proliferation of cells in this neurogenic niche was induced by activation of AT2 receptors but depended partially on the AT2-dependent antagonism of AT1 receptor expression, which restricted proliferation. Furthermore, we observed a functional dependence of AT2 receptor actions on Mas receptors. In rats, where the levels of the AT1 relative to those of AT2 receptor are much lower, pharmacological inhibition of the AT1 receptor alone was sufficient in increasing AT2 receptor levels and proliferation in the V-SVZ. Our data revealed that interactions between RAS receptors play a major role in the regulation of V-SVZ neurogenesis, particularly in proliferation, generation of neuroblasts, and migration to the olfactory bulb, both in young and aged brains, and suggest potential beneficial effects of RAS modulators on neurogenesis.
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PMID:Interaction between Angiotensin Type 1, Type 2, and Mas Receptors to Regulate Adult Neurogenesis in the Brain Ventricular-Subventricular Zone. 3180 Dec 96