Biomedical subjects

Jeff M Sands

Publications and source records attributed to Jeff M Sands.

40 records · Page 3Linked to original sources

PubMed2002

Vasopressin rapidly increases phosphorylation of UT-A1 urea transporter in rat IMCDs through PKA.

The UT-A1 urea transporter plays an important role in maintaining the hyperosmolar milieu of the inner medulla. Vasopressin increases urea permeability in rat terminal inner medullary collecting ducts (IMCDs) within 5-10 min. To elucidate the mechanism, IMCD suspensions were radiolabeled with [(32)P]orthophosphate. UT-A1 was immunoprecipitated and analyzed by autoradiogram and Western blot. Both the 97- and 117-kDa UT-A1 proteins were phosphorylated. Vasopressin treatment increased the phosphorylation of both UT-A1 proteins at 2 min, which peaked at 5-10 min and remained elevated for up to 30 min. There was a discernable increase in UT-A1 phosphorylation with 10 pM and a 50% increase with 10-100 nM vasopressin. 1-Desamino-8-D-arginine vasopressin (dDAVP) or 8-(4-chlorophenylthio)-cAMP (CPT-cAMP) also increased UT-A1 phosphorylation. The vasopressin-stimulated increase in UT-A1 phosphorylation was blocked by H-89 or a specific peptide inhibitor of protein kinase A. Phosphatase inhibitors (okadaic acid, calyculin) increased UT-A1 phosphorylation. We conclude that vasopressin increases UT-A1 phosphorylation via protein kinase A within 2-5 min in rat IMCDs. This suggests that phosphorylation of UT-A1 may be the mechanism by which vasopressin rapidly increases urea permeability in vivo.

Animals↗

PubMed2002

Acidosis mediates the upregulation of UT-A protein in livers from uremic rats.

Liver expresses a 49-kD UT-A protein whose abundance is increased by uremia. Chronic renal failure causes acidosis; therefore, the role of acidosis in increasing UT-A abundance was tested. Rats underwent 5/6 nephrectomy, and half were given bicarbonate mixed in their food. Bicarbonate administration significantly increased blood pH. Compared with sham-operated rats, UT-A protein abundance was significantly increased by 50% in livers from uremic, acidotic rats; bicarbonate administration prevented the increase in UT-A protein. To determine whether acidosis alone would increase UT-A protein in liver, rats were made acidotic, but not uremic, by feeding them HCl. HCl-feeding significantly lowered blood pH, increased urea excretion, and increased the abundance of the 49-kD liver UT-A protein by 36% compared with pair-fed nonacidotic rats. HCl-feeding significantly increased the abundance of the 117-kD UT-A1 protein in kidney inner medulla but did not change aquaporin-2 protein. Next, rats were fed urea to determine whether elevated blood urea would increase UT-A protein. However, urea feeding had no effect on UT-A in liver or kidney inner medulla. It was, therefore, concluded that acidosis, either directly or through a change in ammonium concentration, rather than other dietary components, stimulates the upregulation of UT-A protein in liver and kidney inner medulla.

Acidosis↗

PubMed2002

A prospective evaluation of the glomerular filtration rate in older adults with frequent nighttime urination.

PURPOSE: We assessed the association of renal function with frequent nighttime urination in older adults. MATERIALS AND METHODS: We recruited a convenience sample of 48 adults 65 years old and older, and admitted them to a general clinical research center. Of the 48 participants 45 completed a 7-day voiding record, ate a research diet for 4 days and finished a 3-day stay with 3 glomerular filtration rate measurements, including an estimation of serum creatinine using the Cockcroft-Gault formula, a calculation using 24-hour urine volume and a determination by 131iodine iothalamate clearance. RESULTS: Subjects with frequent nighttime voiding, defined as a mean of 2 or more voiding episodes from 11 p.m. to 7 a.m., had slightly lower but statistically similar glomerular filtration rate measurements than those with a mean of less than 2 nighttime voids. The glomerular filtration rate did not correlate with the number of nighttime voids (Pearson correlation coefficient -0.006, p = 0.971). Mean 24-hour urine output was similar in the 2 groups and the correlation of the number of nighttime voids with 24-hour urine output was insignificant (Pearson correlation coefficient -0.06, p = 0.683). A greater number of nighttime voids was associated with producing more urine at night and smaller mean voided volume. CONCLUSIONS: As determined by a gold standard glomerular filtration rate measurement, renal function was not associated with the number of nighttime voids in our study population. Total 24-hour urine output was also not associated with the number of nighttime voids. Our findings confirmed the positive association of a greater number of nighttime voids with greater nighttime urine production and lower bladder voided volume.

Aged↗

PubMed2000

Differential expression of individual UT-A urea transporter isoforms in rat kidney.

The rat renal urea transporter UT-A includes four mRNA isoforms: UT-A1, UT-A2, UT-A3, and UT-A4. This study detected by rapid amplification of cDNA ends (RACE), primer extension, and ribonuclease protection assay (RPA) a single transcription start site for UT-A1, UT-A3, and UT-A4, distinct from the one for UT-A2 and identified by 3'-RACE new transcripts of UT-A1, UT-A2, and UT-A3, characterized by alternative 3' untranslated sequences (UTR). Expression of an alternative 3'UTR resulted in UT-A1 and UT-A2 transcripts that are approximately 400 bp shorter than the original cDNA. These mRNA isoforms (UT-A1b and UT-A2b) were present in low abundance in the inner medulla. Expression of an alternative 3'UTR for UT-A3 resulted in a 3.5 kb transcript (UT-A3b), which is 1.5 kb longer than the original UT-A3 cDNA. UT-A3b mRNA was easily detected by Northern hybridization in the inner medulla. This study examined whether different states of hydration induce homogeneous changes in mRNA expression of individual UT-A isoforms in the kidney. Analysis of UT-A1, UT-A1b, UT-A2, UT-A2b, UT-A3, and UT-A3b mRNA expression in rat kidney revealed that water deprivation markedly increases the relative abundance of UT-A2, UT-A2b, UT-A3, and UT-A3b mRNA in renal inner medulla, whereas UT-A1 and UT-A1b remain almost unchanged. The conclusion is that differential expression of individual UT-A mRNA isoforms occurs in the kidney and probably involves multiple regulatory mechanisms.

3' Untranslated Regions↗