Ah receptor in spleen of rodent and primate species: detection by binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin

1989 ◽  
Vol 67 (6) ◽  
pp. 594-600 ◽  
Author(s):  
Eve A. Roberts ◽  
Lynn M. Vella ◽  
Cheryl L. Golas ◽  
Leslie A. Dafoe ◽  
Allan B. Okey
Keyword(s):  
Rhesus Monkeys ◽  
Specific Binding ◽  
Velocity Sedimentation ◽  
Primate Species ◽  
Ah Receptor ◽  
Sprague Dawley ◽  
Wasting Syndrome ◽  
Specific Organ ◽  
Tetrachlorodibenzo P Dioxin ◽  
Tcdd Toxicity

In many species systemic toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is manifested by a generalized wasting syndrome accompanied by a variety of specific organ changes including atrophy of the thymus and spleen. TCDD toxicity in most tissues is thought to be mediated by the Ah receptor. Although the spleen is a prime target for TCDD toxicity, the possible presence of Ah receptor in the spleen has not previously been investigated. Specific binding of [3H]TCDD to Ah receptor in spleen cytosols was assessed by velocity sedimentation on sucrose gradients. Ah receptor was detected in spleen cytosols from adult Rhesus monkeys (mean ± SEM, 36 ± 8 fmol/mg cytosol protein), fetal Rhesus monkeys (9 ± 6), Sprague–Dawley rats (20 ± 5), C57BL/6J mice (18 ± 2), New Zealand white rabbits (19 ± 2), and Hartley guinea pigs (15 ± 2). Ah receptor was not detectable in spleen cytosol from genetically "nonresponsive" DBA/2J mice or from Golden Syrian hamsters, a species resistant to toxicity of TCDD. Molecular properties of Ah receptor from spleen were similar to those of the receptor from liver of the same species. The high Ah receptor content in spleen cytosols from those species that are most susceptible to TCDD toxicity is consistent with the view that the Ah receptor mediates TCDD toxicity in spleen as well as in other tissues.Key words: Ah receptor, 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin, immunotoxicity, spleen.

Downregulation of the Ah receptor in mouse hepatoma cells treated in culture with 2,3,7,8-tetrachlorodibenzo-p-dioxin

1991 ◽  
Vol 69 (8) ◽  
pp. 1204-1210 ◽  
Author(s):  
Rebecca D. Prokipcak ◽  
Allan B. Okey
Keyword(s):  
Nuclear Receptor ◽  
Specific Binding ◽  
Hepatoma Cells ◽  
Ah Receptor ◽  
Short Term ◽  
Mouse Hepatoma ◽  
Receptor Sites ◽  
Short Term Exposure ◽  
Cytosolic Extract ◽  
Tetrachlorodibenzo P Dioxin

The aromatic hydrocarbon (Ah) receptor behaves as a ligand-dependent transcription factor in the induction of cytochrome P450IA1. In cells exposed to the Ah receptor ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the Ah receptor undergoes a transformation from a form with low affinity for nucleic acids (cytosolic receptor) into a form that preferentially associates with the cell nucleus (nuclear receptor). We followed the fate of the Ah receptor in mouse hepatoma cells during short-term exposure to [3H]TCDD by analyzing both cytosolic and nuclear fractions for specific binding. Nuclear Ah receptor levels increased over the first 2 h of treatment and then decreased to about 50% of maximal concentrations by 5 h after start of treatment. The decrease in nuclear receptor was not accompanied by a reappearance of detectable Ah receptor in the cytosolic fraction; further incubation with [3H]TCDD in cytosols from lysed cells did not label any additional receptor sites in cytosolic extract. By the 6th h of incubation, the total receptor population in the cell was only about 15–20% of that detected at the start of the incubation. The levels of specific binding detected were unaffected by up to 20 h of incubation with the vehicle DMSO, confirming that the presence of TCDD is required for the observed downregulation to occur. These results indicate that there is a substantial ligand-dependent loss in total Ah receptor during short-term exposure of cells to TCDD in culture.Key words: Ah receptor, 2,3,7,8-tetrachlorodibenzo-p-dioxin, dioxin toxicity, Hepa-1 mouse hepatoma cells.

scholarly journals THE Ah PHENOTYPE. SURVEY OF FORTY-EIGHT RAT STRAINS AND TWENTY INBRED MOUSE STRAINS

Genetics ◽  
1982 ◽  
Vol 100 (1) ◽  
pp. 79-87
Author(s):  
Daniel W Nebert ◽  
Nancy M Jensen ◽  
Hisashi Shinozuka ◽  
Heinz W Kunz ◽  
Thomas J Gill
Keyword(s):  
Specific Activity ◽  
Inbred Mouse ◽  
Inbred Mouse Strain ◽  
Mouse Strains ◽  
Ah Receptor ◽  
Inbred Mouse Strains ◽  
Sprague Dawley ◽  
Rat Strains ◽  
Specific Activities ◽  
Inbred Rat

ABSTRACT Forty-four inbred and four randombred rat strains and 20 inbred mouse strains were examined for their Ah phenotype by determining the induction of liver microsomal aryl hydrocarbon (benzo[a]pyrene) hydroxylase activity (EC 1.14.14.1) by intraperitoneal treatment with either β-naphthoflavone or 3-methylcholanthrene. All 48 rat strains were found to be Ah-responsive. The maximally induced hydroxylase specific activities of the ALB/Pit, MNR/Pit, MR/Pit, SHR/Pit, and Sprague-Dawley strains were of the same order of magnitude as the basal hydroxylase specific activities of the ACI/Pit, F344/Pit, OKA/Pit, and MNR/N strains. Six of the 20 mouse strains were Ah-nonresponsive (i.e. lacking the normal induction response and presumably lacking detectable amounts of the Ah receptor). The basal hydroxylase specific activities of the BDL/N, NFS/N, STAR/N, and ST/JN mouse strains were more than twice as high as the maximally induced hydroxylase specific activity of the CBA/HT strain.——To date, 24 Ah-nonresponsive mouse strains have been identified, out of a total of 68 known to have been characterized. The reasons for not finding a single Ah-nonresponsive inbred rat strain—as compared with about one Ah-nonresponsive inbred mouse strain found for every three examined—remain unknown.

scholarly journals Photoaffinity labeling of the nuclear Ah receptor from mouse Hepa 1c1c7 cells using 2,3,7,8-[3H]tetrachlorodibenzo-p-dioxin

1989 ◽  
Vol 264 (31) ◽  
pp. 18463-18471
Author(s):  
J P Landers ◽  
J Piskorska-Pliszczynska ◽  
T Zacharewski ◽  
N J Bunce ◽  
S Safe
Keyword(s):  
Photoaffinity Labeling ◽  
Ah Receptor ◽  
Tetrachlorodibenzo P Dioxin

Ah receptor involvement in mediation of pyruvate carboxylase levels and activity in mice given 2,3,7,8-tetrachlorodibenzo-p-dioxin

1995 ◽  
Vol 10 (2) ◽  
pp. 103-109 ◽  
Author(s):  
Byung-Woo Ryu ◽  
Shukla Roy ◽  
Barney R. Sparrow ◽  
Daniel P. Selivonchick ◽  
Henry W. Schaup
Keyword(s):  
Pyruvate Carboxylase ◽  
Ah Receptor ◽  
Tetrachlorodibenzo P Dioxin

Androgens augment proximal tubule transport

2004 ◽  
Vol 287 (3) ◽  
pp. F452-F459 ◽  
Author(s):  
Albert Quan ◽  
Sumana Chakravarty ◽  
Jian-Kang Chen ◽  
Jian-Chun Chen ◽  
Samer Loleh ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Specific Binding ◽  
Extracellular Volume ◽  
Renin Angiotensin System ◽  
Angiotensin Receptors ◽  
Sprague Dawley ◽  
Angiotensin System ◽  
Renin Angiotensin

The proximal tubule contains an autonomous renin-angiotensin system that regulates transport independently of circulating angiotensin II. Androgens are known to increase expression of angiotensinogen, but the effect of androgens on proximal tubule transport is unknown. In this in vivo microperfusion study, we examined the effect of androgens on proximal tubule transport. The volume reabsorptive rate in Sprague-Dawley rats given dihydrotestosterone (DHT) injections was significantly higher than in control rats given vehicle injections (4.57 ± 0.31 vs. 3.31 ± 0.23 nl·min−1·mm−1, P < 0.01). Luminally perfusing with either enalaprilat (10−4 M) to inhibit production of angiotensin II or losartan (10−8 M) to block the angiotensin receptor decreased the proximal tubule volume reabsorptive rate in DHT-treated rats to a significantly greater degree than in control vehicle-injected rats. The renal expression of angiotensinogen was shown to be higher in the DHT-treated animals, using Northern blot analysis. The expression of angiotensin receptors, determined by specific binding of angiotensin II, was not different in the two groups of animals. Brush-border membrane protein abundance of the Na/H exchanger, a membrane transport protein under angiotensin II regulation, was also higher in DHT-treated rats vs. control rats. Rats that received DHT had higher blood pressures than the control rats but had no change in their glomerular filtration rate. In addition, serum angiotensin II levels were lower in DHT-treated vs. control rats. These results suggest that androgens may directly upregulate the proximal tubule renin-angiotensin system, increase the volume reabsorptive rate, and thereby increase extracellular volume and blood pressure and secondarily decrease serum angiotensin II levels.

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