Effects ofin VivoExposure to Bis(tri-n-butyltin)oxide, Hexachlorobenzene, and Benzo(a)pyrene on Cytokine (Receptor) mRNA Levels in Cultured Rat Splenocytes and on IL-2 Receptor Protein Levels

1998 ◽  
Vol 148 (1) ◽  
pp. 126-136 ◽  
Author(s):  
Rob J. Vandebriel ◽  
Clive Meredith ◽  
Mary P. Scott ◽  
Paul J.M. Roholl ◽  
Henk Van Loveren
Keyword(s):  
Cytokine Receptor ◽  
Receptor Protein ◽  
Mrna Levels ◽  
Protein Levels ◽  
Receptor Mrna

scholarly journals Genetic Background Underlying 5-HT1A Receptor Functioning Affects the Response to Fluoxetine

2020 ◽  
Vol 21 (22) ◽  
pp. 8784
Author(s):  
Elena M. Kondaurova ◽  
Alexander Ya. Rodnyy ◽  
Tatiana V. Ilchibaeva ◽  
Anton S. Tsybko ◽  
Dmitry V. Eremin ◽  
...  
Keyword(s):  
Genetic Background ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Tryptophan Hydroxylase ◽  
Forced Swim Test ◽  
Receptor Protein ◽  
Mrna Levels ◽  
Tryptophan Hydroxylase 2 ◽  
Protein Levels ◽  
Receptor Mrna ◽  
Fluoxetine Treatment

The influence of genetic background on sensitivity to drugs represents a topical problem of personalized medicine. Here, we investigated the effect of chronic (20 mg/kg, 14 days, i.p.) antidepressant fluoxetine treatment on recombinant B6-M76C mice, differed from control B6-M76B mice by CBA-derived 102.73–110.56 Mbp fragment of chromosome 13 and characterized by altered sensitivity of 5-HT1A receptors to chronic 8-OH-DPAT administration and higher 5-HT1A receptor mRNA levels in the frontal cortex and hippocampus. Significant changes in the effects of fluoxetine treatment on behavior and brain 5-HT system in recombinant B6-M76C mice were revealed. In contrast to B6-M76B mice, in B6-M76C mice, fluoxetine produced pro-depressive effects, assessed in a forced swim test. Fluoxetine decreased 5-HT1A receptor mRNA levels in the cortex and hippocampus, reduced 5-HT1A receptor protein levels and increased receptor silencer Freud-1 protein levels in the hippocampus of B6-M76C mice. Fluoxetine increased mRNA levels of the gene encoding key enzyme for 5-HT synthesis in the brain, tryptophan hydroxylase-2, but decreased tryptophan hydroxylase-2 protein levels in the midbrain of B6-M76B mice. These changes were accompanied by increased expression of the 5-HT transporter gene. Fluoxetine reduced 5-HT and 5-HIAA levels in cortex, hippocampus and midbrain of B6-M76B and in cortex and midbrain of B6-M76C; mice. These data demonstrate that changes in genetic background may have a dramatic effect on sensitivity to classic antidepressants from the Selective Serotonin Reuptake Inhibitors family. Additionally, the results provide new evidence confirming our idea on the disrupted functioning of 5-HT1A autoreceptors in the brains of B6-M76C mice, suggesting these mice as a model of antidepressant resistance.

Glucose regulation of the IGF response system in chondrocytes: induction of an IGF-I-resistant state

1999 ◽  
Vol 276 (4) ◽  
pp. R1164-R1171 ◽  
Author(s):  
K. M. Kelley ◽  
T. R. Johnson ◽  
J. Ilan ◽  
R. W. Moskowitz
Keyword(s):  
Glucose Concentration ◽  
Northern Analysis ◽  
Type I ◽  
Mrna Levels ◽  
Protein Levels ◽  
Receptor Mrna ◽  
Response System ◽  
Type I Igf Receptor ◽  
Igf I ◽  
Igf Receptor

Nonresponsiveness to the growth-stimulatory actions of insulin-like growth factor (IGF)-I in chondrocytes has been reported in a number of disease states associated with impaired glucose metabolism. Primary rabbit chondrocytes were investigated for changes in their IGF response system [type-I IGF receptor and IGF-binding protein (IGFBP) expression] and in their ability to mount a synthetic response to IGF-I [as35S-labeled proteoglycan ([35S]PG) production] in media containing varying ambient glucose concentrations. Whereas basal [35S]PG synthetic rate was unaffected by glucose concentration, synthetic responsiveness to IGF-I was lost in media containing <5 mmol/l glucose or in media containing a “diabetic” glucose concentration (25 mmol/l). IGFBP expression, as measured by Northern analysis of mRNA levels and Western ligand blotting of secreted protein levels, was not significantly altered in the different glucose media, nor were there any differences in the cell surface localization of IGFBPs as assessed by affinity cross-linking with 125I-labeled IGF-I, suggesting that IGFBPs do not induce the IGF-I resistance. The nonresponsiveness to IGF-I in reduced glucose occurred with 25–50% reductions in steady-state levels of IGF type-I receptor mRNA and protein. A significant correlation between IGF receptor mRNA level and synthetic response to IGF-I was observed between 0 and 10 mmol/l glucose concentrations, suggesting that the loss of responsiveness in reduced glucose is manifested at the level of transcription and/or receptor mRNA stability. In contrast, nonresponsiveness to IGF-I in chondrocytes in diabetic glucose concentrations occurred without changes in receptor mRNA and protein levels, suggesting that IGF-I resistance was due to post-ligand-binding receptor defects. It is proposed that IGF-I resistance in chondrocytes subjected to inappropriate glucose levels may constitute an important pathogenic mechanism in degenerative cartilage disorders.

Regulation of rat renal alpha 2 B-adrenergic receptors by potassium depletion

1994 ◽  
Vol 266 (2) ◽  
pp. F316-F324
Author(s):  
J. C. Muir ◽  
L. Huang ◽  
J. K. Harrison ◽  
D. L. Rosin ◽  
M. D. Okusa
Keyword(s):  
Blot Analysis ◽  
Receptor Protein ◽  
Detectable Effect ◽  
Potassium Depletion ◽  
Mrna Levels ◽  
Binding Studies ◽  
Deficient Diet ◽  
Proximal Tubule Cells ◽  
Protein Levels ◽  
Tubule Cells

Potassium depletion and alpha 2-adrenergic receptor (alpha 2-AR) agonists produce similar physiological effects on renal function. Both stimuli increase Na-H exchange in proximal tubule cells, inhibit water transport in collecting tubule cells, and alter blood pressure regulation. The purpose of this study was to determine whether potassium depletion and renal alpha 2-AR subtype expression were linked. Kidney membrane proteins and RNA were harvested from anesthetized rats fed a potassium-deficient diet for 4-20 days (LK 4 to LK 20). Using a selective alpha 2-AR antagonist, [3H]MK-912, we observed that potassium depletion led to a dramatic increase in maximum binding (270% of control) without a change in dissociation constant. Competitive binding studies in LK 14 kidney membranes employing chlorpromazine, prazosin, and oxymetazoline suggested that the increase in alpha 2-ARs in response to potassium depletion was due primarily to an increase in the B subtype of alpha 2-AR. Northern blot analysis demonstrated that renal alpha 2B-AR mRNA levels increased (190% of control) after 4 or 14 days on a potassium-deficient diet. In contrast, there was no difference in steady-state alpha 2A-receptor protein levels by Western blot analysis. We conclude that potassium depletion selectively increases the expression of the B subtype of alpha 2-AR with no detectable effect on alpha 2A-AR expression.

Ontogeny and effect of cortisol on vasopressin-1b receptor expression in anterior pituitaries of fetal sheep

2003 ◽  
Vol 284 (1) ◽  
pp. R51-R56 ◽  
Author(s):  
Sharla F. Young ◽  
Jennifer L. Smith ◽  
Jorge P. Figueroa ◽  
James C. Rose
Keyword(s):  
Receptor Expression ◽  
Late Gestation ◽  
Mrna Levels ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Protein Levels ◽  
Receptor Mrna ◽  
Naturally Occurring ◽  
V1b Receptor

Corticotroph responsiveness to arginine vasopressin (AVP) increases during late gestation in fetal sheep. The mechanism of this increase in AVP responsiveness is currently unknown but could be related to an increase in vasopressin type 1b (V1b) receptor expression in the pituitary during development. To determine if there are ontogenic changes in V1b receptor expression that may help explain the changes in ACTH responses to AVP, we studied pituitaries from three groups of fetal sheep [100, 120, or 140 days gestational age (dGA)]. V1b receptor mRNA and protein significantly decreased by 140 dGA. Peak V1b mRNA levels were detected at 100 dGA, while peak V1b protein levels were detected at 120 dGA. The reduction in V1b receptor expression in late gestation may be due to the naturally occurring peripartum increase in fetal plasma cortisol because cortisol infusion at 122–130 dGA decreased V1b receptor mRNA. Thus there is a marked decrease in the expression of the V1b receptor in the pituitary during fetal development, leaving the role of the V1b receptor in increasing AVP responsiveness uncertain.

Change in β1-adrenergic receptor protein concentration in adipose tissue correlates with diet-induced weight loss

2005 ◽  
Vol 108 (4) ◽  
pp. 323-329 ◽  
Author(s):  
Mads RASMUSSEN ◽  
Anita BELZA ◽  
Thomas ALMDAL ◽  
Søren TOUBRO ◽  
Palle BRATHOLM ◽  
...  
Keyword(s):  
Weight Loss ◽  
Adipose Tissue ◽  
Adrenergic Receptor ◽  
Laser Scanning ◽  
Protein Concentration ◽  
Receptor Protein ◽  
Mrna Levels ◽  
Receptor Mrna ◽  
Β2 Adrenergic Receptor ◽  
Obese Subjects

The aim of the present study was to examine gene expression and protein concentrations of β1- and β2-adrenergic receptors in subcutaneous adipose tissue in obese subjects in response to weight loss. Eighteen obese subjects were studied during diet-induced weight loss. β-Adrenergic receptor mRNA levels were quantified by reverse transcription-PCR–HPLC. β-Adrenergic receptor protein concentrations were measured by Western blotting using fluorescence laser scanning for detection. Subjects lost 12.8±0.8 kg (mean±S.E.M.) during diet treatment. There was a 34% decrease in the β1-adrenergic receptor mRNA level (0.92±0.09 compared with 0.61±0.06 amol/μg of DNA; P<0.002). β2-Adrenergic receptor mRNA did not decrease significantly. β2-Adrenergic receptor protein concentration decreased 37% (25.5±7.1 compared with 16.0±5.6 arbitrary units/ng of DNA; P=0.008), whereas β1-adrenergic receptor protein concentration did not decrease significantly. The degree of weight loss was correlated with the concentration of β1-adrenergic receptor protein (r=0.65, P<0.003) and changes in receptor protein concentration (r=0.50, P=0.035) during the very-low-calorie diet. In conclusion, the present study demonstrates a relationship between β1-adrenergic receptor protein concentration in adipose tissue and the degree of weight loss. This relationship is not directly related to energy expenditure and deserves further investigation.

scholarly journals cAMP-induced desensitization of surface cAMP receptors in Dictyostelium: different second messengers mediate receptor phosphorylation, loss of ligand binding, degradation of receptor, and reduction of receptor mRNA levels.

1992 ◽  
Vol 3 (6) ◽  
pp. 603-612 ◽  
Author(s):  
P J Van Haastert ◽  
M Wang ◽  
A A Bominaar ◽  
P N Devreotes ◽  
P Schaap
Keyword(s):  
Signal Transduction ◽  
Ligand Binding ◽  
Second Messenger ◽  
Receptor Protein ◽  
Mrna Levels ◽  
Receptor Phosphorylation ◽  
Receptor Mrna ◽  
Second Messenger Systems ◽  
Camp Receptor ◽  
No Activation

Surface cAMP receptors on Dictyostelium cells are linked to several second messenger systems and mediate multiple physiological responses, including chemotaxis and differentiation. Activation of the receptor also triggers events which desensitize signal transduction. These events include the following: 1) loss of ligand binding without loss of receptor protein; 2) phosphorylation of the receptor protein, which may lead to impaired signal transduction; 3) redistribution and degradation of the receptor protein; and 4) decrease of cyclic AMP (cAMP) receptor mRNA levels. These mechanisms of desensitization were investigated with the use of mutant synag7, with no activation of adenylyl cyclase; fgdC, with no activation of phospholipase C; and fgdA, with defects in both pathways. cAMP-induced receptor phosphorylation and loss of ligand binding activity was normal in all mutants. In contrast, cAMP-induced degradation of the receptor was absent in all mutants. The cAMP-induced decrease of cAMP-receptor mRNA levels was normal in mutant synag7, but absent in mutant fgdC. Finally, the cAMP analogue (Rp)-cAMPS induced loss of ligand binding without inducing second messenger responses or phosphorylation, redistribution, and degradation of the receptor. We conclude that 1) loss of ligand binding can occur in the absence of receptor phosphorylation; 2) loss of ligand binding and receptor phosphorylation do not require the activation of second messenger systems; 3) cAMP-induced degradation of the receptor may require the phosphorylation of the receptor as well as the activation of at least the synag7 and fgdC gene products; and 4) cAMP-induced decrease of receptor mRNA levels requires the activation of the fgdC gene product and not the synag7 gene product. These results imply that desensitization is composed of multiple components that are regulated by different but partly overlapping sensory transduction pathways.

scholarly journals Advancing age alters the expression of the ryanodine receptor 3 isoform in adult rat superior cervical ganglia

2006 ◽  
Vol 101 (2) ◽  
pp. 392-400 ◽  
Author(s):  
Conwin K. Vanterpool ◽  
Elaine A. Vanterpool ◽  
William J. Pearce ◽  
John N. Buchholz
Keyword(s):  
Ryanodine Receptor ◽  
Molecular Mechanisms ◽  
Calcium Release ◽  
Age Groups ◽  
Molecular Techniques ◽  
Receptor Protein ◽  
Mrna Levels ◽  
Genetic Expression ◽  
Adult Rat ◽  
Protein Levels

Sympathetic nerves arising from the superior cervical ganglion (SCG) protect the cerebrovasculature during periods of acute hypertension and may play a role in homeostasis of target organs. The functions of these nerves depend on calcium release triggered by activation of ryanodine receptor (RyR) channels. The function of RyR channels is in part dependent on genetic expression and regulation by numerous protein modulators such as neuronal nitric oxide synthase (nNOS) neurons also found in the SCG. We have shown that release of calcium in SCG cells is altered during late maturation and advancing age. However, the underlying molecular mechanisms that may in part account for these data are elusive. Therefore we used molecular techniques to test the hypothesis that advancing age alters the pattern of genetic expression and/or protein levels of RyRs and their modulation by nNOS in the SCG in F344 rats aged 6, 12, and 24 mo. Surprisingly, ryr1 expression was undetectable in all age groups and ryr2 and ryr3 are the predominantly transcribed isoforms in the adult rat SCG. mRNA and protein levels for RyR2 isoform did not change with advancing age. However, ryr3 mRNA levels increased from 6 to 12 mo and declined from 12 to 24 mo. Similarly, RyR3 receptor protein levels also increased from 6 to 12 mo and declined from 12 to 24 mo. Because nNOS and the phosphorylation of the RyRs have been shown to modulate the function of RyRs, total phosphorylation and nNOS protein levels were analyzed in all age groups. Phosphorylation levels of the RyRs were similar in all age groups. However, nNOS protein levels increased from 6 to 12 mo followed by decline from 12 to 24 mo. These data suggest that advancing age selectively impacts the genetic expression and protein levels of RyR3 as well as modulatory nNOS protein levels. In addition, these data may part provide some insight into the possible changes in the function of RyRs that may occur with the normal aging process.

scholarly journals Expression of the putative cannabinoid receptor GPR55 is increased in endometrial carcinoma

2021 ◽  
Author(s):  
Thangesweran Ayakannu ◽  
Anthony H. Taylor ◽  
Justin C. Konje
Keyword(s):  
Endometrial Cancer ◽  
Therapeutic Target ◽  
Cannabinoid Receptor ◽  
Receptor Protein ◽  
Mrna Levels ◽  
Rt Pcr ◽  
Transcript Levels ◽  
Protein Levels

AbstractAlthough the expression of the putative cannabinoid receptor GPR55 has been shown to be involved in the growth of various tumours and is increased in a number of cancers, its expression has not been examined in patients with endometrial cancer (EC). Quantitative RT-PCR (for mRNA levels) and immunohistochemistry (for protein levels) were used to measure GPR55 expression in patients with Type 1 and Type 2 EC and correlated against cannabinoid receptor (CB1 and CB2) protein levels using non-cancerous endometrium as the control tissue. The data indicated that GPR55 transcript and GPR55 protein levels were significantly (p < 0.002 and p < 0.0001, respectively) higher in EC tissues than in control tissues. The levels of immunoreactive GPR55 protein were correlated with GPR55 transcript levels, but not with the expression of CB1 receptor protein, and were inversely correlated with CB2 protein expression, which was significantly decreased. It can be concluded that GPR55 expression is elevated in women with EC, and thus could provide a potential novel biomarker and therapeutic target for this disease.

Effects of hyperoxia on VEGF, its receptors, and HIF-2α in the newborn rat lung

2003 ◽  
Vol 285 (1) ◽  
pp. L161-L168 ◽  
Author(s):  
Gayle E. Hosford ◽  
David M. Olson
Keyword(s):  
Hypoxia Inducible Factor ◽  
Treated Group ◽  
Receptor Protein ◽  
Vegf Receptor ◽  
Mrna Levels ◽  
Signaling System ◽  
Vegf Mrna ◽  
Receptor System ◽  
Protein Levels ◽  
Vegf Signaling

Signaling through the hypoxia inducible factor (HIF)-VEGF-VEGF receptor system (VEGF signaling system) leads to angiogenesis and epithelial cell proliferation and is a key mechanism regulating alveolarization in lungs of newborn rats. Hyperoxia exposure (>95% O2 days 4–14) arrests lung alveolarization and may do so through suppression of the VEGF signaling system. Lung tissue mRNA levels of HIF-2α and VEGF increased from days 4–14 in normoxic animals, but hyperoxia suppressed these increases. Levels of HIF-2α and VEGF mRNA were correlated in the air but not the O2-treated group, suggesting that the low levels of HIF-2α observed at high O2 concentrations are not stimulating VEGF expression. VEGF164 protein levels increased with developmental age, and with hyperoxia to day 9, but continuing hyperoxia decreased levels by day 12. VEGFR1 and VEGFR2 mRNA expression also increased in air-exposed animals, and these, too, were significantly decreased by hyperoxia by day 9 and day 12, respectively. Receptor protein levels did not increase with development; however, O2 did decrease protein to less than air values. Hyperoxic suppression of VEGF signaling from days 9–14 may be one mechanism by which alveolarization is arrested.

scholarly journals Quinapril decreases renal endothelin-1 expression and synthesis in a normotensive model of immune-complex nephritis.

1997 ◽  
Vol 8 (5) ◽  
pp. 756-768
Author(s):  
M Ruiz-Ortega ◽  
D Gómez-Garre ◽  
X H Liu ◽  
J Blanco ◽  
R Largo ◽  
...  
Keyword(s):  
Immune Complex ◽  
Ace Inhibitors ◽  
Ace Inhibitor ◽  
Mrna Levels ◽  
Ang Ii ◽  
Endothelin 1 ◽  
Protein Levels ◽  
Receptor Mrna ◽  
Eta Receptor ◽  
Ace Activity

Angiotensin-converting enzyme (ACE) inhibitors diminish proteinuria and the progression to renal failure in several experimental models of renal injury. Endothelin-1 (ET-1) possesses potent biological actions on renal vessels and has been considered as a potential mediator of renal damage. Because angiotensin II (Ang II) induces ET-1 synthesis in endothelial and mesangial cells, we hypothesized that some of the beneficial effects of the ACE inhibitors could result from the blockade of ET-1 synthesis. In a normotensive model of immune-complex nephritis, in which there exists an increase in renal ACE activity, the effect of the ACE inhibitor quinapril on preproET-1 and ETA receptor mRNA expression, as well as on ET-1 protein levels, was examined in this study. In relation to controls, nephritic rats showed an increase in preproET-1 and ETA receptor gene expression in renal cortex and medulla, coinciding with the maximal renal ACE activity. PreproET-1 mRNA (in situ hybridization) and ET-1 protein (immunohistochemistry) were localized in glomerular capillary walls, mesangial and glomerular epithelial cells, as well as in the brush border of some proximal tubules, and in small vessels. In nephritic rats, there was an increase in preproET-1 mRNA levels and ET-1 protein in all of these areas, without modification of their distribution. The administration of the ACE inhibitor quinapril decreased proteinuria and morphological lesions, preproET-1 gene transcription, and ET-1 protein levels, as well as the ETA receptor mRNA. The results from this study show that in a normotensive model of immune-complex nephritis, there was an overexpression of ET-1 in several structures of the kidney that was downregulated by quinapril administration. The beneficial effect of ACE inhibitors could be a result of the modulation of local production of Ang II and ET-1.

Sign in / Sign up

Export Citation Format

Share Document