INT84595

Context Info Confidence 0.58 First Reported 1999 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 11 Total Number 15 Disease Relevance 4.88 Pain Relevance 1.78

aging (Aqp2) plasma membrane (Aqp2) protein complex (Aqp2) transmembrane transport (Aqp2) lysosome (Aqp2) cytoplasm (Aqp2)

Anatomy Link Frequency urine 4 inner medulla 2 kidney 2 ascending limb 1 duct 1 Aqp2 (Rattus norvegicus)

Pain Link Frequency Relevance Heat Clonidine 18 99.36 hyperexcitability 1 95.36 agonist 9 84.56 antagonist 26 47.52 ischemia 2 38.56 anesthesia 15 25.00 Neuritis 1 21.44 withdrawal 15 5.00 alcohol 10 5.00 isoflurane 8 5.00

Disease Link Frequency Relevance Heat Renal Disease 50 99.76 Aging 7 99.76 Chronic Renal Failure 313 99.60 Hypertrophy 30 99.42 Hyperthyroidism 5 99.26 Diabetes Insipidus 15 98.92 Adrenal Insufficiency 10 97.34 Volume Depletion And Dehydration 5 89.80 Syndrome 5 87.28 Cirrhosis 10 86.76

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

The increase in free water clearance with clonidine administration was associated with a reduction in whole kidney AQP-2 mRNA levels (282+/-25 versus 216+/-11 A units, p<.05).

Negative_regulation (reduction) of AQP-2 in kidney associated with clonidine

1) Confidence 0.58 Published 1999 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 10525117 Disease Relevance 0 Pain Relevance 0.58

In the present study, we demonstrated that 1) CRF rats treated with candesartan were associated with decreased kidney weight and increased BUN level compared with CRF rats treated with vehicle; 2) CRF rats, both candesartan-treated and vehicle-treated, demonstrated decreased AQP2 levels in remnant kidneys and this was likely to play a role in the decreased urine concentration.

Negative_regulation (decreased) of AQP2 in urine associated with chronic renal failure

2) Confidence 0.55 Published 2005 Journal Journal of Korean Medical Science Section Body Doc Link PMC2808601 Disease Relevance 1.22 Pain Relevance 0

This decrease in water reabsorption was associated with a redistribution of AQP-2 away from the luminal membrane of the medullary collecting duct to the cytosol.

Negative_regulation (redistribution) of AQP-2 in duct

3) Confidence 0.42 Published 1999 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 10525117 Disease Relevance 0 Pain Relevance 0.58

RESULTS: Polyuria and increased natriuresis were seen 6 h after LPS injection alongside downregulation of both AQP2 and S256-phosphorylated AQP2 in CTX/OSOM and ISOM but not in inner medulla (IM).

Negative_regulation (downregulation) of AQP2 in inner medulla

4) Confidence 0.41 Published 2009 Journal Nephrol. Dial. Transplant. Section Body Doc Link 19193739 Disease Relevance 0 Pain Relevance 0

CONCLUSIONS: Early downregulation of AQP2 and sodium transporters takes place segmentally in the kidney after LPS administration.

Negative_regulation (downregulation) of AQP2 in kidney

5) Confidence 0.41 Published 2009 Journal Nephrol. Dial. Transplant. Section Body Doc Link 19193739 Disease Relevance 0 Pain Relevance 0

RESULTS: Polyuria and increased natriuresis were seen 6 h after LPS injection alongside downregulation of both AQP2 and S256-phosphorylated AQP2 in CTX/OSOM and ISOM but not in inner medulla (IM).

Negative_regulation (downregulation) of AQP2 in inner medulla

6) Confidence 0.41 Published 2009 Journal Nephrol. Dial. Transplant. Section Body Doc Link 19193739 Disease Relevance 0 Pain Relevance 0

In conclusion, 1) candesartan treatment in an early phase of CRF is associated with decreased renal hypertrophy and increased BUN level; 2) decreased AQP2 level in CRF is likely to play a role in the decreased urine concentration, and the downregulation is not altered in response to candesartan treatment; 3) candesartan treatment decreases NHE3 and TSC expression; and 4) an increase of BSC-1 is prominent in candesartan-treated CRF rats, which could be associated with the increased delivery of sodium and water to the thick ascending limb.

Negative_regulation (decreased) of AQP2 in ascending limb associated with hypertrophy and chronic renal failure

7) Confidence 0.40 Published 2005 Journal Journal of Korean Medical Science Section Abstract Doc Link PMC2808601 Disease Relevance 1.79 Pain Relevance 0

The rapid redistribution of AQP-2 and the reduction in AQP-2 mRNA following clonidine administration are consistent with the hypothesis that the alpha(2) adrenoceptor regulates water excretion at least in part by effects on AQP-2.

Negative_regulation (reduction) of AQP-2 associated with clonidine

8) Confidence 0.37 Published 1999 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 10525117 Disease Relevance 0 Pain Relevance 0.57

Thus, an abnormal up- or downregulation of the aquaporin2 water channels in the principal cells seems to be an important patophysiological factor in development of concentrating and diluting defects in progressive renal disesase [3,9-11].

Negative_regulation (downregulation) of aquaporin2

9) Confidence 0.37 Published 2010 Journal BMC Nephrol Section Body Doc Link PMC2965705 Disease Relevance 0.17 Pain Relevance 0

L-NIL co-treatment prevented the downregulation of NKCC2 but not AQP2 in LPS rats.

Negative_regulation (downregulation) of AQP2

10) Confidence 0.36 Published 2009 Journal Nephrol. Dial. Transplant. Section Body Doc Link 19193739 Disease Relevance 0 Pain Relevance 0

Our results are in agreement with a previous small study of patients with diabetic nephropathy, in whom a decrease in u-AQP2 was associated with impaired urinary concentrating ability [20].

Negative_regulation (decrease) of AQP2 associated with renal disease

11) Confidence 0.31 Published 2010 Journal BMC Nephrol Section Body Doc Link PMC2965705 Disease Relevance 0.39 Pain Relevance 0

U-AQP2 was reduced during urine dilution in all groups, but the level was higher in Group 4 that in the other three groups during the whole test.

Negative_regulation (reduced) of AQP2 in urine

12) Confidence 0.27 Published 2010 Journal BMC Nephrol Section Body Doc Link PMC2965705 Disease Relevance 0.17 Pain Relevance 0

In addition, urine diluting capacity is reduced in hypothyreoidism and adrenal insufficiency with up regulation of AQP2 [4-6], and urine concentration capacity is reduced in thyrotoxicosis and glucocorticoid excess with down regulation of AQP2 [7,8].

Negative_regulation (regulation) of AQP2 in urine associated with hyperthyroidism and adrenal insufficiency

13) Confidence 0.27 Published 2010 Journal BMC Nephrol Section Body Doc Link PMC2965705 Disease Relevance 0.94 Pain Relevance 0

U-AQP2 decreased during urine diluting test in all groups.

Negative_regulation (decreased) of AQP2 in urine

14) Confidence 0.27 Published 2010 Journal BMC Nephrol Section Body Doc Link PMC2965705 Disease Relevance 0 Pain Relevance 0

In addition, the expression of several aquaporins including AQP1, AQP2, AQP3, and AQP5 decrease with aging [49–51], and therefore AQP4 expression may also decrease with aging.

Negative_regulation (decrease) of AQP2 associated with aging

15) Confidence 0.09 Published 2008 Journal Molecular Vision Section Body Doc Link PMC2559817 Disease Relevance 0.20 Pain Relevance 0.05

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