Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuropeptide Y (NPY) and peptide YY (PYY) are structurally related peptides that primarily function as neurotransmitter and gastrointestinal hormone, respectively. Previous functional and binding data have indicated the existence of at least three distinct receptor types, Y1, Y2, and Y3, for NPY and/or PYY in mammals. We describe here a human Y1 cDNA clone, hY1-5, isolated from a fetal brain library. The human Y1 receptor consists of 384 amino acids and has seven putative transmembrane domains like other members of the G-protein-coupled superfamily of receptors. In the region spanning the transmembrane domains, the Y1 receptor displays 29% sequence identity to human tachykinin receptors, but it only shows 21% and 23% homology with proposed bovine (LCR1) and Drosophila (PR4) NPY receptor clones, respectively. Northern blot analysis of a human neuroblastoma cell line, SK-N-MC, previously used by many investigators as a model system for studies on the Y1 receptor, revealed a single 3.5-kilobase mRNA species. Reverse transcriptase-polymerase chain reaction analysis indicated expression also in human cultured vascular smooth muscle cells, supporting the view that the Y1 receptor is associated with NPY/PYY-evoked vasoconstriction. When expressed in COS1 cells, hY1-5 conferred specific 125I-PYY binding sites with displacement patterns characteristic of the Y1 receptor, i.e. PYY greater than or equal to NPY greater than or equal to [Leu31,Pro34]NPY much greater than NPY2-36 greater than C2NPY greater than pancreatic polypeptide greater than NPY13-36 greater than NPY18-36. Moreover, in the Y1 receptor-transfected COS1 cells, but not in type 1 angiotensin II receptor-transfected control cells, NPY and PYY accelerated 45Ca2+ influx and inhibited forskolin-stimulated cAMP accumulation, both phenomena being characteristic of the mammalian Y1 receptor.
 ...
PMID:Cloning and functional expression of a human neuropeptide Y/peptide YY receptor of the Y1 type. 131 48

At least two distinct genes (AT1A and AT1B) encode type 1 angiotensin II (AT1) receptors in rodents. Receptor binding and Northern blot analysis have clearly demonstrated the presence of AT1 receptors and AT1-receptor mRNA in many tissues but fail to differentiate which type 1 receptor subtype is expressed. A reverse-transcriptase polymerase chain reaction restriction fragment length polymorphism (RT-PCR-RFLP) assay was developed to differentiate the expressed mRNA by subtype. Expression of AT1A was clearly evident in kidney, liver, adrenal gland, ovary, brain, testes, adipose tissue, lung, and heart of adult mice. AT1B was absent from most of these tissues but was detectable in brain, testes, and adrenal gland. No significant differences in expression were evident in kidney, liver, brain, lung, or heart from 16.5- or 18.5-gestation-day fetuses, and only AT1A was evident in placenta. Expression of AT1B was confirmed in adrenal gland, brain, and testes, using a primer set that specifically amplifies only AT1B mRNA. Expression of AT1A and AT1B was also examined in As4.1 cells, a renin-expressing mouse kidney tumoral cell line. Receptor binding and competition assays using AT1- and AT2-receptor antagonists revealed that only AT1 receptors are present on the cell surface. Extremely low levels of AT1-receptor mRNA was detected by Northern blot, and RT-PCR-RFLP analysis revealed that only the AT1A subtype is expressed in this cell line. Despite the high homology between the coding sequence of the AT1A and AT1B genes, they exhibit disparate tissue-specific expression profiles.
 ...
PMID:Differential expression of angiotensin receptor 1A and 1B in mouse. 807 5

To determine the possible involvement of the central angiotensin system in hypertension, the angiotensin II type-1 receptor subtype mRNA levels in the preoptic area (POA) and hypothalamus were measured by means of a reverse-transcriptase/polymerase chain reaction in spontaneously hypertensive rats (SHR), and the results were then compared with the findings in age-matched normotensive Wistar-Kyoto rats (WKY). In 4-week-old (prehypertensive stage) and 7-week-old (evolving stage) SHR, the AT1A and AT1B receptor subtype mRNA levels in the POA and hypothalamus did not show any significant difference between the SHR and WKY. However, in the 16-week-old SHR (hypertensive stage), AT1A receptor subtype mRNA at POA was approximately 2-fold higher than in the WKY, while the AT1B receptor subtype mRNA showed no difference. On the other hand, neither the AT1A nor the AT1B mRNA level at the hypothalamus were different between the 16-week-old SHR and WKY. These results suggest that the AT1A mRNA level, but not the AT1B mRNA level, increases in the POA in hypertensive stage of SHR and the increase may therefore be related in some way to the state of hypertension.
 ...
PMID:The developmental increase of the AT1A, but not the AT1B, receptor mRNA level at the preoptic area in spontaneously hypertensive rats. 861 62

In this study, the mouse neuroblastoma cell line Neuro-2a was analyzed for expression of angiotensin II receptors. Reverse-transcriptase polymerase chain reaction (RT-PCR) showed that Neuro-2a cells express mRNA of angiotensin II (AngII) receptor subtypes AT1A, AT1B, and AT2. Analysis of Neuro-2a cells by Western blotting revealed AT1 and AT2 receptor protein expression. The predominant molecular weights were determined to be 50.4 kDa for the AT1 receptor and 62.4 kDa for the AT2 receptor. Observation of AT1 and AT2 receptor localization within Neuro-2a cells using immunocytochemistry showed distribution similar to other G-protein coupled receptors with diffuse distribution in the cytosol, perinuclear enrichment and accumulation of receptors on the outer cellular periphery with extension into the neurites. Furthermore, we observed InsP3 formation following AngII induction that could be abolished in presence of the AT1A receptor antagonist losartan. The results clearly show expression of the AngII receptor types AT1A and AT2 in the Neuro-2a cell line. We conclude that Neuro-2a cells represent an interesting model cell line for study of mechanisms that control the interplay between these receptors.
 ...
PMID:Angiotensin II receptor types 1A, 1B, and 2 in murine neuroblastoma Neuro-2a cells. 1268 May 93