Growth hormone regulates ammoniagenesis in canine renal proximal tubule segments

1992 ◽  
Vol 262 (5) ◽  
pp. F878-F884 ◽  
Author(s):  
M. C. Chobanian ◽  
C. M. Julin ◽  
K. H. Molteni ◽  
P. C. Brazy
Keyword(s):  
Growth Hormone ◽  
Atpase Activity ◽  
Proximal Tubule ◽  
Human Growth ◽  
Glucose Production ◽  
Renal Proximal Tubule ◽  
Ammonia Production ◽  
Physiological Conditions ◽  
Dose Dependent ◽  
Proximal Tubule Segments

To determine whether growth hormone (GH) directly affects ammoniagenesis in the renal proximal tubule, ammonia production was measured in suspensions of isolated canine renal proximal tubule segments (IPTs) incubated with 2.5 mM L-glutamine and varying concentrations of human growth hormone (hGH). Ammonia production from IPTs significantly increased by nearly threefold in the presence of hGH (10(-6) M) at 60 min. This increase was dose dependent, with as little as 10(-9) M hGH significantly stimulating ammonia production. In addition, hGH enhanced glucose production when lactate, alanine, and succinate replaced L-glutamine as substrate. hGH significantly stimulated ammonia production when IPTs were incubated at alkalotic and neutral pH. The effect of hGH was lost at acidic pH. When hGH was added to IPTs incubated under Na(+)-equilibrated conditions, ammonia production was not different from control. hGH stimulated ouabain-sensitive Na(+)-K(+)-adenosinetriphosphatase (ATPase) activity by 8.1 +/- 1.1% in basolateral membranes isolated from IPTs. hGH stimulation of proximal tubule ammonia production from L-glutamine occurs at physiological concentrations of hGH and when the extracellular-to-intracellular Na+ gradient favors L-glutamine transport. This effect is associated with an increase in basolateral Na(+)-K(+)-ATPase activity. The data suggest a role for hGH in the regulation of renal acid-base metabolism under physiological conditions in which increased net acid excretion is important.

Angiotensin II stimulates ammoniagenesis in canine renal proximal tubule segments

1991 ◽  
Vol 260 (1) ◽  
pp. F19-F26 ◽  
Author(s):  
M. C. Chobanian ◽  
C. M. Julin
Keyword(s):  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Glucose Production ◽  
Renal Proximal Tubule ◽  
Ang Ii ◽  
Ammonia Production ◽  
Proximal Tubule Segments ◽  
Dependent Pathway ◽  
Stimulation Of

To determine whether angiotensin II (ANG II) affects ammoniagenesis in renal proximal tubule, ammonia production was measured in suspensions of canine renal proximal tubule segments (PCT) incubated with L-glutamine and varying concentrations of ANG II. Ammonia production from PCT was significantly increased by 15.5 +/- 1.1% in the presence of ANG II (10(-6) M) at 2 h. Similarly, glucose production significantly increased by 10.0 +/- 0.9%. Half-maximal stimulation occurred at approximately 10(-9) M ANG II. Stimulation of ammonia production by ANG II was blocked in the presence of the ANG II antagonist, [Sar1-Ile8]ANG II (10(-6) M). Enhancement of ammonia production in PCT by ANG II occurred in acidotic and neutral media but not in alkalotic medium. When extracellular [Na+] = intracellular [Na+] ANG II significantly increased ammonia production in PCT. Absence of extracellular Ca2+ or addition of trifluoperazine or N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7) (Ca2(+)-calmodulin-dependent pathway inhibitors) blocked the action of ANG II to enhance ammonia production. We conclude that ANG II stimulates ammonia and glucose production in canine renal PCT via a receptor-mediated signal. The action of ANG II on ammoniagenesis may be mediated by a calcium-calmodulin-dependent pathway. Stimulation of ammoniagenesis in vitro under normal and acidotic conditions may reflect a role in vivo for ANG II in the regulation of renal acid-base metabolism.

Growth hormone directly stimulates gluconeogenesis in canine renal proximal tubule

1989 ◽  
Vol 257 (5) ◽  
pp. E751-E756
Author(s):  
S. A. Rogers ◽  
I. E. Karl ◽  
M. R. Hammerman
Keyword(s):  
Growth Hormone ◽  
Proximal Tubule ◽  
Glucose Production ◽  
Renal Proximal Tubule ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Igf I ◽  
Proximal Tubular

To characterize the action of growth hormone (GH) on gluconeogenesis in renal proximal tubule, glucose production was measured in suspensions of canine renal proximal tubular segments incubated with 1 mM L-alanine, 10 mM lactate, 1 mM succinate, and various concentrations (10(-11) to 10(-6) M) of recombinant bovine GH (bGH). Production of glucose increased as a function of time for 120 min. Bovine growth hormone (10(-6) M) increased glucose production at 120 min by 55 +/- 16%. Significant enhancement of glucose production occurred in suspensions of segments incubated with as little as 10(-10) M bGH. Half-maximal stimulation occurred at between 10(-9) and 10(-8) M. To ascertain whether these actions of bGH are mediated directly, we determined the effects of insulin-like growth factors (IGFs) I and II on glucose production. Addition of IGF-I to segments enhanced glucose production in a concentration-dependent manner. However, incubation with bGH did not induce measurable IGF-I production in the segments. In contrast to the action of IGF-I, IGF-II did not affect glucose production. We conclude that bGH acts directly on cells within proximal tubular segments to enhance gluconeogenesis. Stimulation of gluconeogenesis in vitro could reflect a counterregulatory action of GH exerted on renal proximal tubule in vivo.

High-salt diet upregulates activity and mRNA of renal Na(+)-K(+)-ATPase in Dahl salt-sensitive rats

1993 ◽  
Vol 264 (3) ◽  
pp. F448-F452 ◽  
Author(s):  
A. Nishi ◽  
G. Celsi ◽  
A. Aperia
Keyword(s):  
Atpase Activity ◽  
Proximal Tubule ◽  
Hormonal Regulation ◽  
High Salt ◽  
Dopa Decarboxylase ◽  
Primary Defect ◽  
High Salt Diet ◽  
Salt Diet ◽  
Tubular Cells ◽  
Proximal Tubule Segments

We examined the effect of a high-salt (HS) diet on the regulation of renal cortical Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) in young Dahl salt-sensitive (DS) and salt-resistant (DR) rats. The activity of Na(+)-K(+)-ATPase, determined in permeabilized proximal tubule segments, was similar in DS and DR rats on normal salt (NS) diet. HS diet resulted in a twofold increase in proximal tubule Na(+)-K(+)-ATPase activity in DS rats but not in DR rats. The mRNA abundance, which was also similar in DS and DR rats on NS diet, increased after 2 days on HS diet in both innervated and denervated kidneys from DS rats but had no effect in DR rats. The activity of Na(+)-K(+)-ATPase and the content of alpha 1- and beta-protein in cortical homogenate were similar in DS and DR rats on both NS and HS diets. Treatment with benserazide, an inhibitor of dopa decarboxylase, upregulated proximal tubule Na(+)-K(+)-ATPase activity and increased Na(+)-K(+)-ATPase mRNA in DR rats on HS diet. Taken together, these data indicate that there is a primary defect in the dynamic hormonal regulation of Na(+)-K(+)-ATPase activity in intact tubular cells, which might stimulate Na(+)-K(+)-ATPase transcription.

scholarly journals Ammonia production and secretion by S3 proximal tubule segments from acidotic mice: role of ANG II

2004 ◽  
Vol 287 (4) ◽  
pp. F707-F712 ◽  
Author(s):  
Glenn T. Nagami
Keyword(s):  
Proximal Tubule ◽  
Ang Ii ◽  
Ammonia Production ◽  
Low Sodium ◽  
Luminal Perfusion ◽  
And Control ◽  
Acid Loading ◽  
Proximal Tubule Segments ◽  
Secretion Rates

ANG II has potent effects on ammonia production and secretion rates by the proximal tubule and is found in substantial concentrations in the lumen of the proximal tubule in vivo. Because our previous studies demonstrated that acid loading enhanced the stimulatory effects of ANG II on ammonia production and secretion by S2 proximal tubule segments, we examined the effect of ANG II on ammonia production and secretion by isolated, perfused S3 segments from nonacidotic control mice and acidotic mice given NH4Cl for 7 days. In the absence of ANG II, ammonia production and secretion rates were no different in S3 segments from acidotic and control mice. By contrast, when ANG II was present in the luminal perfusion solution, ammonia production and secretion rates were stimulated, in a losartan-inhibitable manner, to a greater extent in S3 segments from acidotic mice. Ammonia secretion rates in S3 segments were largely inhibited by perfusion with a low-sodium solution containing amiloride in the presence or absence of ANG II. These results demonstrated that isolated, perfused mouse S3 proximal tubule segments produce and secrete ammonia, that NH4Cl-induced acidosis does not affect the basal rates of ammonia production and secretion, and that ANG II, added to the luminal fluid, stimulates ammonia production and secretion to a greater extent in S3 segments from acidotic mice. These findings suggest that S3 segments, in the presence of ANG II, can contribute to the enhanced renal excretion that occurs with acid loading.

Expression of calcineurin activity and alpha-subunit isoforms in specific segments of the rat nephron

1995 ◽  
Vol 269 (4) ◽  
pp. F558-F563 ◽  
Author(s):  
J. A. Tumlin ◽  
J. T. Someren ◽  
C. E. Swanson ◽  
J. P. Lea
Keyword(s):  
Atpase Activity ◽  
Proximal Tubule ◽  
Proximal Tubules ◽  
Alpha Subunit ◽  
Specific Substrate ◽  
Fk 506 ◽  
Collecting Ducts ◽  
Subunit Isoforms ◽  
Proximal Tubule Segments ◽  
Calcineurin Activity

Calcineurin activity and alpha-subunit expression were studied in microdissected proximal tubules (S2), medullary thick ascending limbs (MTAL), cortical collecting ducts (CCD), connecting tubules (CNT), and outer medullary collecting ducts (OMCD). We have shown that cyclosporin A (CsA) and FK-506 inhibit sodium-potassium-adenosinetriphosphatase (Na-K-ATPase) activity in CCD, OMCD, and MTAL but did not uncover the mechanism for resistance of proximal tubule segments to these drugs. Because cells expressing high calcineurin activity are relatively resistant to the biological effects of CsA and FK-506, we hypothesized that the resistance of proximal tubules may be linked to increased calcineurin expression. Consequently, we measured calcineurin activity in microdissected tubules using a calcineurin-specific substrate. Calcineurin activity in S2 proximal tubule segments was 10-fold higher than in CCD, CNT, OMCD, or MTAL. FK-506 (6.0 ng/ml) inhibited calcineurin activity in CCD, CNT, and MTAL but not S2; 250 ng/ml FK-506 inhibited S2 calcineurin activity by 50%. Likewise, high concentrations of CsA (25 micrograms/ml) and FK-506 (250 ng/ml) inhibited S2 Na-K-ATPase activity by 77 and 73%, respectively. To investigate whether the resistance of S2 segments might be due to differential expression of calcineurin alpha-subunit isoforms, we determined the isoform expression by Western blot analysis using isoform-specific antibodies against the alpha 1-, alpha 2-, and alpha 3-isoforms. We found that alpha 1 expression in S2 was significantly greater than in the CCD and MTAL, whereas alpha 2 expression in the S2 was significantly less than in CCD and MTAL. No alpha 3 was detected in any nephron segment tested.(ABSTRACT TRUNCATED AT 250 WORDS)

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