GABA-A Function and Receptor Binding in the Paraventricular Nucleus in Chronic Renal Wrap Hypertension

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 701-701
Author(s):  
Joseph R Haywood ◽  
Teresa Craig ◽  
Julie Hensler ◽  
Carmen Hinojosa-Laborde
Keyword(s):  
Arterial Pressure ◽  
Paraventricular Nucleus ◽  
Receptor Binding ◽  
Binding Sites ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
Gaba A ◽  
Gaba Binding ◽  
In Vivo Autoradiography

P48 The onset of renal wrap hypertension is associated with a reduced tonic GABA inhibition in the paraventricular nucleus (PVN) on the sympathetic nervous system. This reduced functional inhibition occurs without a change in GABA-A receptor binding in the PVN. The goal of the present study was to determine if GABAergic transmission and GABA binding is altered in chronic renal wrap hypertensive rats. Sprague-Dawley rats were made hypertensive or sham-operated. Four weeks later, animals were prepared with femoral artery catheters for the measurement of arterial pressure. Subgroups were also prepared with bilateral cannulae directed at the PVN. The renal wrap rats had higher mean arterial pressure (MAP): 139±4 mmHg vs.113±2 mmHg, but heart rate (HR) was not different (354±12 bpm vs. 369±6 bpm) as compared to control animals. Administration of the GABA-A antagonist, bicuculline, into the PVN caused a greater increase in MAP and HR in wrap animals (25±2 mmHg and 150±30 bpm) compared to sham operated rats (16±2 mmHg and 89±12 bpm). GABA-A binding sites in the PVN were estimated using in vivo autoradiography. [3H]-Flunitrazepam was used as the receptor ligand. Magnocellular neurons of the PVN showed a higher density of receptors than other areas of the nucleus. However, the number of binding sites was not different between normotensive and hypertensive rats in either the high density (1825±56 vs. 1756±41 fmol/mg protein) or low density (1454±26 vs. 1433±57 fmol/mg protein) regions of PVN. These data indicate that the inhibition by GABA in the PVN is augmented in the chronic stage of hypertension, and appears to be unrelated to a change in the number of GABA binding sites. The increased GABAergic inhibition is in contrast to the reduced inhibition that has been observed during the onset of hypertension.

Decreased hexokinase activity in paraventricular nucleus of adult SHR and renal hypertensive rats

1988 ◽  
Vol 254 (3) ◽  
pp. R508-R512 ◽  
Author(s):  
T. L. Krukoff
Keyword(s):  
Arterial Pressure ◽  
Paraventricular Nucleus ◽  
Metabolic Activity ◽  
Central Nucleus ◽  
Hypothalamic Nucleus ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
Medial Nucleus ◽  
Wistar Kyoto ◽  
Renal Hypertensive Rats

Metabolic activity was assessed in the brains of spontaneously hypertensive rats (SHR) using the histochemical hexokinase (HK) technique and photodensitometric analysis. Of eight regions known to play a role in cardiovascular regulation, only the paraventricular nucleus of the hypothalamus (PVH) exhibited alterations in HK activity. Significantly lower levels of HK activity in SHR than in control Sprague-Dawley and Wistar-Kyoto rats were measured in both the parvo- and magnocellular divisions of the PVH. No differences in HK activity were found in the anterior hypothalamic nucleus, posterior hypothalamic nucleus, supraoptic nucleus, subfornical organ, central nucleus of the amygdala, or the medial nucleus of the tractus solitarius of SHR. Similar results were obtained in renal hypertensive rats; furthermore, a positive correlation was found between levels of arterial pressure and densitometric readings. These latter results strongly suggest that metabolic alterations in the PVH of SHR are directly related to the increases in arterial pressure and are not due to the genetic makeup of SHR. In light of studies by others, the data from the present study have been interpreted to suggest that the decreases in metabolic activity in the PVH of the adult SHR are the result of a central attempt to bring the level of the arterial pressure down to normal levels and not to the altered activity of a region that might be acting to keep arterial pressure elevated.

scholarly journals Androgen and glucocorticoid receptor direct distinct transcriptional programs by receptor-specific and shared DNA binding sites

2021 ◽  
Vol 49 (7) ◽  
pp. 3856-3875
Author(s):  
Marina Kulik ◽  
Melissa Bothe ◽  
Gözde Kibar ◽  
Alisa Fuchs ◽  
Stefanie Schöne ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Transcription Factor ◽  
Dna Binding ◽  
Receptor Binding ◽  
Binding Sites ◽  
Specific Gene ◽  
Functional Diversification ◽  
Enhancer Activity ◽  
Sequence Composition

Abstract The glucocorticoid (GR) and androgen (AR) receptors execute unique functions in vivo, yet have nearly identical DNA binding specificities. To identify mechanisms that facilitate functional diversification among these transcription factor paralogs, we studied them in an equivalent cellular context. Analysis of chromatin and sequence suggest that divergent binding, and corresponding gene regulation, are driven by different abilities of AR and GR to interact with relatively inaccessible chromatin. Divergent genomic binding patterns can also be the result of subtle differences in DNA binding preference between AR and GR. Furthermore, the sequence composition of large regions (>10 kb) surrounding selectively occupied binding sites differs significantly, indicating a role for the sequence environment in guiding AR and GR to distinct binding sites. The comparison of binding sites that are shared shows that the specificity paradox can also be resolved by differences in the events that occur downstream of receptor binding. Specifically, shared binding sites display receptor-specific enhancer activity, cofactor recruitment and changes in histone modifications. Genomic deletion of shared binding sites demonstrates their contribution to directing receptor-specific gene regulation. Together, these data suggest that differences in genomic occupancy as well as divergence in the events that occur downstream of receptor binding direct functional diversification among transcription factor paralogs.

scholarly journals Further evidence against the role renal medullary perfusion in short-term control of arterial pressure in normotensive and mildly or overtly hypertensive rats

2021 ◽  
Vol 473 (4) ◽  
pp. 623-631
Author(s):  
Bożena Bądzyńska ◽  
Iwona Baranowska ◽  
Janusz Sadowski
Keyword(s):  
Arterial Pressure ◽  
Renal Excretion ◽  
Sodium Concentration ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
Critical Determinant ◽  
Human Hypertension ◽  
Pressure Elevation ◽  
Doppler Probe ◽  
Medullary Tissue

AbstractEarlier evidence from studies of rat hypertension models undermines the widespread view that the rate of renal medullary blood flow (MBF) is critical in control of arterial pressure (MAP). Here, we examined the role of MBF in rats that were normotensive, with modest short-lasting pressure elevation, or with overt established hypertension. The groups studied were anaesthetised Sprague-Dawley rats: (1) normotensive, (2) with acute i.v. norepinephrine-induced MAP elevation, and (3) with hypertension induced by unilateral nephrectomy followed by administration of deoxycorticosterone-acetate (DOCA) and 1% NaCl drinking fluid for 3 weeks. MBF was measured (laser-Doppler probe) and selectively increased using 4-h renal medullary infusion of bradykinin. MAP, renal excretion parameters and post-experiment medullary tissue osmolality and sodium concentration were determined. In the three experimental groups, baseline MAP was 117, 151 and 171 mmHg, respectively. Intramedullary bradykinin increased MBF by 45%, 65% and 70%, respectively, but this was not associated with a change in MAP. In normotensive rats a significant decrease in medullary tissue sodium was seen. The intramedullary bradykinin specifically increased renal excretion of water, sodium and total solutes in norepinephrine-treated rats but not in the two other groups. As previously shown in models of rat hypertension, in the normotensive rats and those with acute mild pressure elevation (resembling labile borderline human hypertension), 4-h renal medullary hyperperfusion failed to decrease MAP. Nor did it decrease in DOCA-salt model mimicking low-renin human hypertension. Evidently, within the 4-h observation, medullary perfusion was not a critical determinant of MAP in normotensive and hypertensive rats.

scholarly journals Two Populations of Glucocorticoid Receptor-Binding Sites in the Male Rat Hippocampal Genome

Endocrinology ◽  
2013 ◽  
Vol 154 (5) ◽  
pp. 1832-1844 ◽  
Author(s):  
J. Annelies E. Polman ◽  
E. Ronald de Kloet ◽  
Nicole A. Datson
Keyword(s):  
Receptor Binding ◽  
Binding Sites ◽  
Glucocorticoid Receptors ◽  
Full Range ◽  
Male Rat ◽  
Motif Analysis ◽  
Wide Range ◽  
Neuronal Processes ◽  
Almost All

Abstract In the present study, genomic binding sites of glucocorticoid receptors (GR) were identified in vivo in the rat hippocampus applying chromatin immunoprecipitation followed by next-generation sequencing. We identified 2470 significant GR-binding sites (GBS) and were able to confirm GR binding to a random selection of these GBS covering a wide range of P values. Analysis of the genomic distribution of the significant GBS revealed a high prevalence of intragenic GBS. Gene ontology clusters involved in neuronal plasticity and other essential neuronal processes were overrepresented among the genes harboring a GBS or located in the vicinity of a GBS. Male adrenalectomized rats were challenged with increasing doses of the GR agonist corticosterone (CORT) ranging from 3 to 3000 μg/kg, resulting in clear differences in the GR-binding profile to individual GBS. Two groups of GBS could be distinguished: a low-CORT group that displayed GR binding across the full range of CORT concentrations, and a second high-CORT group that displayed significant GR binding only after administering the highest concentration of CORT. All validated GBS, in both the low-CORT and high-CORT groups, displayed mineralocorticoid receptor binding, which remained relatively constant from 30 μg/kg CORT upward. Motif analysis revealed that almost all GBS contained a glucocorticoid response element resembling the consensus motif in literature. In addition, motifs corresponding with new potential GR-interacting proteins were identified, such as zinc finger and BTB domain containing 3 (Zbtb3) and CUP (CG11181 gene product from transcript CG11181-RB), which may be involved in GR-dependent transactivation and transrepression, respectively. In conclusion, our results highlight the existence of 2 populations of GBS in the rat hippocampal genome.

A comparison of in vivo and in vitro neuroimaging of 5-HT1A receptor binding sites in the cat brain

2006 ◽  
Vol 31 (3) ◽  
pp. 226-232 ◽  
Author(s):  
Nicolas Aznavour ◽  
Latifa Rbah ◽  
Lucienne Léger ◽  
Colette Buda ◽  
Jean-Pierre Sastre ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Binding Sites ◽  
Cat Brain

scholarly journals Decreased density of GABA-A receptors in the left sensorimotor cortex in akinetic catatonia: investigation of in vivo benzodiazepine receptor binding

1999 ◽  
Vol 67 (4) ◽  
pp. 445-450 ◽  
Author(s):  
G. Northoff ◽  
R. Steinke ◽  
C. Czcervenka ◽  
R. Krause ◽  
S. Ulrich ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Sensorimotor Cortex ◽  
Benzodiazepine Receptor ◽  
Gaba A

scholarly journals Substance P receptor binding sites are expressed by glia in vivo after neuronal injury.

1989 ◽  
Vol 86 (13) ◽  
pp. 5193-5197 ◽  
Author(s):  
P. W. Mantyh ◽  
D. J. Johnson ◽  
C. G. Boehmer ◽  
M. D. Catton ◽  
H. V. Vinters ◽  
...  
Keyword(s):  
Substance P ◽  
Receptor Binding ◽  
Binding Sites ◽  
Neuronal Injury ◽  
Substance P Receptor

scholarly journals Research Resource: Genome-Wide Mapping of in Vivo Androgen Receptor Binding Sites in Mouse Epididymis

2010 ◽  
Vol 24 (12) ◽  
pp. 2392-2405 ◽  
Author(s):  
Shuanggang Hu ◽  
Guangxin Yao ◽  
Xiaojun Guan ◽  
Zimei Ni ◽  
Wubin Ma ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Receptor Binding ◽  
Binding Sites ◽  
Genome Wide ◽  
Mouse Epididymis

scholarly journals Newt epidermal cell migration in vitro and in vivo appears to involve Arg-Gly-Asp-Ser receptors

1987 ◽  
Vol 87 (4) ◽  
pp. 525-534
Author(s):  
D.J. Donaldson ◽  
J.T. Mahan ◽  
G.N. Smith
Keyword(s):  
Receptor Binding ◽  
Binding Sites ◽  
Wound Closure ◽  
Type I Collagen ◽  
Attachment Site ◽  
Epidermal Cells ◽  
Type I ◽  
Human Fibrinogen ◽  
Skin Explants

The effect of a synthetic peptide consisting of Arg-Gly-Asp-Ser (RGDS), the amino acid sequence representing the fibroblast attachment site in fibronectin (FN), was tested on migrating newt epidermal cells. In one approach, skin explants were placed on the bottom of plastic dishes coated with human FN, human fibrinogen (FGN), human serum spreading factor (SF), or bovine type I collagen. The explants were then incubated overnight in serum-free medium with or without RGDS. In these experiments exposure to 50 micrograms ml-1 of RGDS reduced migration over FN, FGN and SF to 2–7% of control levels. Two peptides structurally dissimilar to RGDS (Val-Gly-Ser-Glu and Thr-Pro-Arg-Lys), and two that are structurally similar (Lys-Gly-Asp-Ser and Arg-Gly-Glu-Ser), had no effect on explant migration even when used at concentrations higher than 50 micrograms ml-1. Upon removal of the RGDS peptide, inhibited explants quickly recovered. In collagen-coated dishes 50 micrograms ml-1 of RGDS was much less effective than in dishes coated with the other substrates. Raising the RGDS concentration in collagen-coated dishes tenfold did not greatly increase the RGDS effect. When added to the medium bathing wounded limbs, 50 micrograms ml-1 of RGDS only moderately inhibited wound closure. This concentration of peptide, however, severely inhibited migration from skin explants in newt-plasma-coated-dishes and migration over pieces of newt-plasma-coated plastic placed under one edge of a skin wound. Increasing the RGDS concentration to 500 micrograms ml-1 resulted in almost total suppression of wound closure. Wounds exposed to this same concentration of Lys-Gly-Asp-Ser closed normally. These results indicate that newt epidermal cells possess RGDS receptors and that these receptors are involved in epidermal wound closure in vivo and in migration from skin explants onto plastic coated with FN, FGN, SF and collagen. The relative RGDS-insensitivity of wound closure in vivo and in migration from explants onto collagen may reflect in these instances the presence of a relatively high density of RGDS receptor binding sites on the substrate; the presence of RGDS receptor binding sites of relatively high affinity; or the participation of receptors other than those involved in migration over plastic coated with FN, FGN or SF.

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