Tubular reabsorption of α-aminoisobutyric acid in the pre-steady-state. Evidence for a cell-to-lumen flux

1980 ◽  
Vol 58 (5) ◽  
pp. 557-563 ◽  
Author(s):  
Roderick R. McInnes ◽  
Fazl Mohyuddin ◽  
Charles R. Scriver

We investigated time-dependent and concentration-dependent renal handling of α-aminoisobutyric acid (AIB) in the rat during seven consecutive 30-min clearance periods after onset of AIB infusion. Following low-level rapid venous infusion of AIB (9.75 μmol/kg in 30 s), plasma [AIB] fell exponentially in the initial three periods and in linear fashion (−0.00158 μM/min) thereafter. Although filtered AIB fell in proportion to plasma [AIB] during the early clearance periods (5–125 min), fractional excretion of AIB (FEAIB) rose (Δ FEAIB = +0.077 ± 0.010, mean ± SD) and stabilized only in later clearance periods (125–215 min). Saturable intrarenal binding does not explain rising FEAIB with falling plasma [AIB] because sequential infusions of AIB, 120 min apart, also elicited the phenomenon after each infusion. During continuous infusions of AIB, time dependence of FEAIB was also observed, in the early interval (5–95 min), after onset of AIB infusion at various concentrations of plasma [AIB] below 3 mM approximately. Measurement of concentration-dependent net tubular reabsorption of AIB in the fourth through seventh clearance periods (near the steady state) revealed progressive saturation over the whole range of plasma [AIB] (0–12 mM), yet with a collapse of net reabsorption in the plasma [AIB] range 2–4 mM. Measurements of renal tissue AIB in these experiments revealed that cellular AIB is of sufficient magnitude and bears such a relationship to plasma AIB and FEAIB that it could contribute to an observable cell-to-lumen movement of amino acid in the "pre-steady-state" situation and could account for the rise in FEAIB following AIB infusion and the collapse in tubular reabsorption of AIB at 2–4 mM plasma [AIB].

DICP ◽  
1989 ◽  
Vol 23 (12) ◽  
pp. 1013-1017 ◽  
Author(s):  
Gregory L. Kearns ◽  
Phillip L. Berry ◽  
Joseph A. Bocchini ◽  
Bettina C. Hilman ◽  
John T. Wilson

We evaluated the renal handling of beta2-microglobulin (β2-M) and creatinine in healthy outpatients (n = 6), normal children hospitalized for infections treated with antibiotics (not including an aminoglycoside) (n = 4); outpatients with cystic fibrosis (CF; n = 12), and hospitalized patients with CF (n = 6) who received a 10- to 14-day course of antibiotic treatment that included an aminoglycoside. The serum β2-M concentrations in the normal outpatients (2020.1 ± 276.6 μg/L) were significantly lower (p <0.05) than those observed for outpatients (2833.3 ± 202.6 μg/L) or patients with CF (2861.8 ± 340.5 μg/L. There were no significant differences found for creatinine clearance or fractional excretion of β2-M when subjects without CF were compared with those with the disease. Furthermore, no significant differences were observed in hospitalized patients with CF when creatinine clearance and fractional excretion of β2-M were compared between the initiation and conclusion of aminoglycoside treatment. Glomerular filtration and proximal tubular reabsorption of β2-M were not altered in patients with CF. These findings do not support a global defect in proximal renal tubular reabsorption as the underlying cause for altered aminoglycoside clearance in patients with CF.


Pharmacology ◽  
2021 ◽  
pp. 1-5
Author(s):  
Yuichi Uwai ◽  
Tomohiro Nabekura

Lithium, administered to patients of bipolar disorders, is mainly excreted into urine, and tubular reabsorption at the proximal tubule is involved in the renal handling of lithium. In this study, we examined the renal excretion of lithium in rats with Fanconi syndrome, characterized by defects of transports of various compounds at the proximal tubules, induced by maleic acid. After maleic acid was intravenously injected, mannitol and lithium chloride were infused in turn. Using samples of plasma and bladder urine during the mannitol infusion, renal parameters were determined. Pharmacokinetic parameters of lithium were obtained using samples during the lithium chloride infusion. Maleic acid decreased creatinine clearance and increased the fractional excretion of glucose and phosphate, suggesting the induction of Fanconi syndrome. In rats with Fanconi syndrome, plasma concentration of lithium was increased, and its renal clearance was decreased. No effect on the fractional excretion of lithium was exhibited. This study represents that the tubular reabsorption of lithium was impaired to the same degree with glomerular filtration in rats with experimental Fanconi syndrome and that the dysfunction of the tubular reabsorption of glucose and phosphate was more severe. It is possible that Fanconi syndrome inhibited the reabsorption of lithium at the proximal tubule and facilitated the reabsorption of lithium from the loop of Henle to the collecting duct.


RSC Advances ◽  
2021 ◽  
Author(s):  
Guanzhao Wen ◽  
Xianshao Zou ◽  
Rong Hu ◽  
Jun Peng ◽  
Zhifeng Chen ◽  
...  

Ground- and excited-states properties of N2200 have been studied by steady-state and time-resolved spectroscopies as well as time-dependent density functional theory calculations.


2004 ◽  
Vol 422 (1) ◽  
pp. 173-183 ◽  
Author(s):  
Alexander Romanenko ◽  
Igor Pinkevich ◽  
Victor Reshetnyak ◽  
Ivan Dozov ◽  
Daniel Stoenescu

1988 ◽  
Vol 8 (5) ◽  
pp. 1957-1969 ◽  
Author(s):  
R A Shapiro ◽  
D Herrick ◽  
R E Manrow ◽  
D Blinder ◽  
A Jacobson

As an approach to understanding the structures and mechanisms which determine mRNA decay rates, we have cloned and begun to characterize cDNAs which encode mRNAs representative of the stability extremes in the poly(A)+ RNA population of Dictyostelium discoideum amoebae. The cDNA clones were identified in a screening procedure which was based on the occurrence of poly(A) shortening during mRNA aging. mRNA half-lives were determined by hybridization of poly(A)+ RNA, isolated from cells labeled in a 32PO4 pulse-chase, to dots of excess cloned DNA. Individual mRNAs decayed with unique first-order decay rates ranging from 0.9 to 9.6 h, indicating that the complex decay kinetics of total poly(A)+ RNA in D. discoideum amoebae reflect the sum of the decay rates of individual mRNAs. Using specific probes derived from these cDNA clones, we have compared the sizes, extents of ribosome loading, and poly(A) tail lengths of stable, moderately stable, and unstable mRNAs. We found (i) no correlation between mRNA size and decay rate; (ii) no significant difference in the number of ribosomes per unit length of stable versus unstable mRNAs, and (iii) a general inverse relationship between mRNA decay rates and poly(A) tail lengths. Collectively, these observations indicate that mRNA decay in D. discoideum amoebae cannot be explained in terms of random nucleolytic events. The possibility that specific 3'-structural determinants can confer mRNA instability is suggested by a comparison of the labeling and turnover kinetics of different actin mRNAs. A correlation was observed between the steady-state percentage of a given mRNA found in polysomes and its degree of instability; i.e., unstable mRNAs were more efficiently recruited into polysomes than stable mRNAs. Since stable mRNAs are, on average, "older" than unstable mRNAs, this correlation may reflect a translational role for mRNA modifications that change in a time-dependent manner. Our previous studies have demonstrated both a time-dependent shortening and a possible translational role for the 3' poly(A) tracts of mRNA. We suggest, therefore, that the observed differences in the translational efficiency of stable and unstable mRNAs may, in part, be attributable to differences in steady-state poly(A) tail lengths.


1995 ◽  
Vol 14 (6) ◽  
pp. 494-499 ◽  
Author(s):  
CJ Lote ◽  
JA Wood ◽  
A. Thewles ◽  
M. Freeman

The known toxicity of aluminium, and the toxicity of agents (such as desferrioxamine) used to remove alumini um from the body, has prompted us to investigate whether there may be ways of enhancing aluminium excretion by exploiting the normal renal handling of aluminium. Aluminium (as sulphate or citrate) was administered intravenously to conscious rats at doses ranging from 25 μg (0.93 μmol) to 800 μg (29.6 μmol) aluminium, and alu minium excretion was monitored over the following 2 h. Measurements of the filterability of aluminium from the rat plasma, and the glomerular filtration rate (inulin clearance), enabled us to calculate the filtered load of alu minium, and hence determine aluminium reabsorption. At all doses of administered aluminium, that adminis tered as sulphate was excreted less effectively than that administered as citrate. This difference was attributable to the much greater filterability of aluminium administered as citrate. However, for any given filtered load, the excre tion of aluminium administered as citrate was not signifi cantly different (in either fractional or absolute terms) from the excretion of aluminium administered as sulphate. It seems likely that, following aluminium sulphate administration, the filtered aluminium may be an alumini um citrate form which is then reabsorbed in the same way as aluminium administered as citrate. It is thus apparent that aluminium removal from the body could be further enhanced if it were possible to pre vent the tubular reabsorption of the aluminium species which is so effectively filtered following aluminium citrate administration.


1991 ◽  
Vol 11 (11) ◽  
pp. 5398-5409
Author(s):  
J W Innis ◽  
R E Kellems

An elongation block to RNA polymerase II transcription in exon 1 is a major regulatory step in expression of the murine adenosine deaminase (ADA) gene. Previous work in the laboratory identified abundant short transcripts with 3' termini in exon 1 in steady-state RNA from injected oocytes. Using a cell-free system to investigate the mechanism of premature 3' end formation, we found that polymerase II generates prominent ADA transcripts approximately 96 to 100 nucleotides in length which are similar to the major short transcripts found in steady-state RNA from oocytes injected with ADA templates. We have determined that these transcripts are the processed products of 108- to 112-nucleotide precursors. Precursor formation is (i) favored in reactions using circular templates, (ii) not the result of a posttranscriptional processing event, (iii) sensitive to low concentrations of Sarkosyl, and (iv) dependent on a factor(s) which is inactivated in crude extracts at 47 degrees C for 15 min. The cell-free system will allow further characterization of the template and factor requirements involved in the control of premature 3' end formation by RNA polymerase II.


1976 ◽  
Vol 231 (4) ◽  
pp. 1033-1038 ◽  
Author(s):  
GM Schoepfle

Repetitive stimulation of a single medullated nerve fiber of Xenopus yields a succession of postspike voltage-time curves which are nearly coincident until attainment of a voltage that corresponds to that of the maximum attained by the normal postspike undershoot. Initially the interspike potential returns toward a resting level after this brief phase of hyperpolarization. However, as tetanization proceeds, a pattern of hyperpolarization develops with the result that, in the tetanic steady state, there exists a progressive hyperpolarization throughout each interspike interval. Extent of postspike hyperpolarization in terms of a deviation deltaVm from the resting level of membrane potential is approximated by the variation deltaVm = delta[MNa + MK]/[GNa + GK] where MNa and MK are current densities associated with active pumping of sodium and potassium ions and GNa and GK are corresponding time-dependent leak conductances. Tetanic hyperpolarization is reversibly abolished by cyanide and by exposure to lithium Ringer. Eventual reappearance of tetanic hyperpolarization in the presence of lithium Ringer suggests lithium pumping.


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