Sources of Cyclic Nucleotides in Plasma

Wehmann, Robert E.; Blonde, Lawrence; Steiner, Alton L.

doi:10.1172/jci107535

Cited by 59 publications

(20 citation statements)

References 14 publications

(16 reference statements)

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“…As in humans, urinary clearance accounted for only 15 (19). A balance between uptake and secretion of cyclic nucleotide by the liver may account for the observation reported in the accompanying paper (7), that there is no large concentration difference of cAMP between hepatic artery, superior mesenteric vein, and hepatic vein.…”

Section: Discussionmentioning

confidence: 71%

“…Our investigation of the clearance of plasma cyclic nucleotides by the kidney in the dog were prompted by the observation that cyclic nucleotide concentration in renal venous plasma was substantially less than that in arterial plasma (7). We have shown that in the dog the plasma cyclic nucleotides are also in a dynamic steady state.…”

Section: Discussionmentioning

confidence: 99%

“…Freshly drawn blood was immediately transferred to heparinized centrifuge tubes and mixed well. After centrifugation of blood for 3-5 min at 1,500 g, 2.0 ml of plasma were added to 2.0 ml of 10%o trichloroacetic acid (TCA) and prepared for analysis of unlabeled cyclic nucleotides, as described in our companion paper (7). In preliminary studies, when urine was added directly into the radioimmunoassay, it was observed that in urine from an occasional dog there had occurred some degradation of endogenous cAMP and cGMP.…”

Section: Methodsmentioning

confidence: 99%

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Plasma Clearance Rates and Renal Clearance of 3H-labeled Cyclic AMP and 3H-labeled Cyclic GMP in the Dog

Blonde¹,

Wehmann²,

Steiner³

1974

J. Clin. Invest.

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A B S T R A C T Previously, in an attempt to understand the mechanisms involved in the regulation of plasma cyclic nucleotides, we measured concentrations of adenosine 3',5'-monophosphate (cAMP) and guanosine 3',5'-monophosphate (cGMP) in plasma from selected blood vessels of anesthetized dogs. The observation that the renal venous plasma concentrations of both cyclic nucleotides were less than arterial concentrations suggested that the kidney might be an important site for the elimination of these compounds from plasma and prompted further investigation of the renal handling of these compounds.Tracer doses of either [3H]cAMP or [3H]cGMP were administered to anesthetized dogs by constant intravenous infusion, and metabolic clearance rates were determined. Concentrations of endogenous cyclic nucleotide and of cyclic nucleotide radioactivity were measured in aortic and renal venous plasma as well as in urine. Renal venous plasma [3H]cGMP was 39% and ['H]cAMP was 65% of the concentration in arterial plasma. Endogenous cyclic nucleotide levels showed a similar relationship. The plasma clearance rates (PCR) were 271 ±27 ml/min (mean+SE) for cGMP and 261+17 for cAMP. The total kidney clearance (calculated as the renal plasma flow X renal cyclic nucleotide extraction ratio) accounted for 52+4% and 30±2% of the PCR for cGMP and cAMP, respectively. Only about two-thirds of the total kidney clearance of each cyclic nucleotide could be accounted for by urinary excretion, the remainder presumably being the result of renal metabolism.The urinary clearances of 8H-labeled cGMP (40.9± 4.2 ml/min) and endogenous cGMP (45.0±2.3 ml/min) were not significantly different from each other. Both were approximately 50% greater than the glomerular filtration rate, which was 27.1±2.0 ml/min, indicating that a significant amount of urinary cGMP is derived from plasma by tubular secretion.In contrast, the urinary clearances of 'H-labeled cAMP (23.7±1.9 ml/min) and endogenous cAMP (27.2±2.6 ml/min) were nearly equal both to each other and to the glomerular filtration rate, which was 24.6±+1.7 ml/min. Thus, in the dog, glomerular filtration of plasma cAMP appears to be responsible for most of the cAMP found in urine. Renal production of cAMP, which in humans contributes from a third to a half of the urinary cAMP, was quantitatively of minor importance in the dog.Thus, under the conditions of these experiments in dogs, renal elimination appears to be responsible for half of the PCR of cGMP and about a third of the PCR of cAMP. About a third of the renal elimination of both cyclic nucleotides appears to be due to metabolic degradation within the kidney, and the balance is due to excretion in the urine. INTRODUCTIONThe presence of adenosine 3',5'-monophosphate (cAMP) and guanosine 3', Broadus, Kaminsky, Hardman, Sutherland, and Liddle (6). They demonstrated that both cAMP and cGMP in human plasma have a rapid turnover rate. In their experiments, urinary excretion accounted for only 15-20% of the elimination of each nucleotide from plasma, with...

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Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Plasma Clearance Rates and Renal Clearance of 3H-labeled Cyclic AMP and 3H-labeled Cyclic GMP in the Dog

Blonde¹,

Wehmann²,

Steiner³

1974

J. Clin. Invest.

Self Cite

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“…There is no established theory for the origins of c-AMP and c-GMP in plasma, though exten sive studies in this problem were reported by Wehmann, (1974). Nevertheless, it is generally considered that plasma cyclic nucleotides re flected their concentrations within cells to some extent, and diffusion of these cyclic nucleotides through the cell membrane was actually observed.…”

Section: Discussionmentioning

confidence: 99%

Cyclic Nucleotides in Progressive Muscular Dystrophy

Kito¹,

Yamamoto²,

Itoga³

et al. 1979

Eur Neurol

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The authors radioimmunoassayed cyclic nucleotide concentrations in plasma and biopsied muscles of muscular dystrophy and muscles of chicken embryo. c-AMP concentrations in plasma were significantly lowered in Duchenne-type muscular dystrophy and this lowered degree was correlated with the stage of progression. Plasma c-GMP levels were also depressed in Duchenne-type dystrophy. In biopsied muscles, c-AMP concentrations per milligram of non-collagen protein were within normal limits. Therefore, the decrease of plasma c-AMP concentrations might be an expression of total metabolic changes rather than a pathologic process of the muscle itself. As for the dystrophic chicken embryo, both c-AMP and GMP concentrations were decreasing in the pectoral muscles in parallel with the advancement of hatching stages.

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“…By substituting 0.120 liter/min for kidney clearance (3) and using other normal values from Table III, it can be seen that if metabolic clearance and production were unchanged, the absence of kidney clearance would result in a concentration of cyclic AMP equal to: 13.6 X (0.624 -0.120)-1= 27 nM. support the finding of the present study that a reduction in glomerular filtration rate cannot entirely account for the degree of elevation of plasma cyclic AMP. Recently, Wehmann, Blonde, and Steiner (28,29), using infusions of tritiated cyclic nucleotides in dogs, observed that urinary excretion accounted for only about two-thirds of the total kidney clearance of cyclic AMP, extraction of the nucleotide by renal parenchymal tissue apparently accounting for the remainder. A significant role of renal extraction, in contrast to excretion, was also demonstrated by the experiments of Coulson, RochRamel, and Bowman, who studied the disappearance of ['H]cyclic AMP from plasma before and after nephrectomy in rats (30) and by those of Coulson and Bowman (31), who studied the handling of extracellular cyclic AMP by the perfused rat kidney.…”

Section: Discussionmentioning

confidence: 99%

Studies of the elevated extracellular concentration of cyclic AMP in uremic man.

Hamet¹,

Stouder²,

Ginn³

et al. 1975

J. Clin. Invest.

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A B S T R A C T This study was designed to elucidate the mechanism of elevation of plasma cyclic AMP in uremic man. Plasma cyclic AMP was measured in 15 normal subjects and in 18 patients with severe renal failure. In some members from both groups the kinetic parameters of the metabolism of extracellular cyclic AMP were measured.Plasma cyclic AMP was elevated from 23 nM in control subjects to 59 nM in uremic patients, regardless of the presence or absence of the kidneys or parathyroid glands. A single pass of uremic blood through a Kiil hemodialyzer decreased plasma cyclic AMP from 58 to 30 nM. The clearance of cyclic AMP by the dialyzer correlated directly with the blood flow passing through the machine. Hemodialysis for 6 h decreased plasma cyclic AMP levels in the systemic circulation by only 12%. Studies with tritiated cyclic AMP revealed a plasma clearance rate of 624 ml/min in normal subjects and of 344 ml/min in patients with uremia. Such a large decrease in plasma clearance rate cannot be explained by a failure of urinary excretion of cyclic AMP and suggests impairment of "metabolic clearance." In addition, the "plasma production rate" of cyclic AMP was 65% higher in patients with renal failure than in normal subjects.It is concluded that the elevation of plasma cyclic AMP in uremic man is due to a combination of: (a) lack of urinary excretion, (b) decreased metabolic clearance, and (c) increased production of plasma cyclic AMP.

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Sources of Cyclic Nucleotides in Plasma

Cited by 59 publications

References 14 publications

Plasma Clearance Rates and Renal Clearance of 3H-labeled Cyclic AMP and 3H-labeled Cyclic GMP in the Dog

Plasma Clearance Rates and Renal Clearance of 3H-labeled Cyclic AMP and 3H-labeled Cyclic GMP in the Dog

Cyclic Nucleotides in Progressive Muscular Dystrophy

Studies of the elevated extracellular concentration of cyclic AMP in uremic man.

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