Arginine vasopressin metabolism in dogs. I. Evidence for a receptor-mediated mechanism.

1978 ◽  
Vol 235 (6) ◽  
pp. E591 ◽  
Author(s):  
R E Weitzman ◽  
D A Fisher
Keyword(s):  
Arginine Vasopressin ◽  
Urine Osmolality ◽  
Volume Of Distribution ◽  
Membrane Receptors ◽  
Constant Infusion ◽  
Metabolic Clearance ◽  
Strong Negative Correlation ◽  
Pulse Injection ◽  
Plasma Membrane Receptors ◽  
Infusion Technique

The plasma clearance rates (PCR) of arginine vasopressin (AVP), and iodinated AVP (125I-AVP) were determined after pulse injection in conscious water-loaded dogs. Both the PCR and the apparent initial volume of distribution were significantly greater for AVP than for the biologically inactive iodinated AVP 37.4 +/- 4.8 ml/kg per min vs. 6.7 +/- 0.8 ml/kg per min (P less than 0.001) and 12.7 +/- 0.9% body wt vs. 7.1 +/- 0.4% body wt (P less than 0.001). AVP clearance was then determined by the constant-infusion technique at doses that produced equilibrium AVP concentrations within and above the physiological range. AVP-PCR was 37.4 +/- 7.1 ml/kg per min at 34 microU/kg per min, which was comparable to that after pulse injection (P less than 0.9). AVP clearance fell progressively, and urine osmolality progressively increased with increasing AVP infusion rates to plateau values at 136 microU/kg per min; a strong negative correlation was observed between mean AVP-PCR and urine osmolality (r = -0.993). The data suggest a relationship between the biological activity of AVP and its clearance. It is proposed that plasma membrane receptors may mediate a portion of the metabolic clearance of AVP.

A Comparative Study on the Metabolism of Human Insulin and Porcine Proinsulin in Man

1973 ◽  
Vol 45 (5) ◽  
pp. 633-654 ◽  
Author(s):  
P. H. Sönksen ◽  
Christine V. Tompkins ◽  
M. C. Srivastava ◽  
J. D. N. Nabarro
Keyword(s):  
Human Insulin ◽  
Normal Subjects ◽  
Constant Infusion ◽  
Metabolic Clearance ◽  
Priming Dose ◽  
Metabolic Clearance Rate ◽  
Serum Growth Hormone ◽  
Biological Potency ◽  
Infusion Technique ◽  
Apparent Distribution

1. The metabolism of unlabelled monocomponent human insulin and porcine proinsulin was studied in ten normal subjects (five males and five females) by using a priming dose-constant-infusion technique. In each subject, the metabolic clearance rate (MCR) was measured at four separate steady-state hormone concentrations averaging 16–216 μunits/ml (insulin) and 4·2–42·8 ng/ml (proinsulin). 2. For insulin the MCR fell progressively from 34 ml kg−1 min−1 at a mean fasting insulin concentration of 3·8 μunits/ml to 11·4 ml kg−1 min−1 at the highest concentration achieved (280 μunits/ml); for proinsulin MCR averaged 3·7 ml kg−1 min−1 at a mean plasma concentration of 4·2 ng/ml and fell to 2·71 ml kg−1 min−1 at 10·7 ng/ml, remaining constant thereafter at concentrations up to 71 ng/ml. 3. The half-disappearance time (T½) from the plasma, after the end of the infusion, averaged 4·3 min for insulin and 25·6 min for proinsulin. 4. The apparent distribution space (DS) was similar for both hormones (83 ml/kg of insulin and 98·9 ml/kg of proinsulin). 5. There was a direct correlation between T½ and DS for both hormones. 6. Although the higher MCR of insulin was reflected in its shorter T½ there was, for each hormone, no relationship between MCR and T½. 7. The biological potency of porcine proinsulin, as judged by its effect on plasma glucose, was approximately 5% of that of insulin. 8. The responses of serum growth hormone and Cortisol were shown to be directly related to the degree of hypoglycaemia induced.

Assessment of methods for improving tracer estimation of non-steady-state rate of appearance

1999 ◽  
Vol 87 (5) ◽  
pp. 1813-1822 ◽  
Author(s):  
A. Gastaldelli ◽  
A. R. Coggan ◽  
R. R. Wolfe
Keyword(s):  
Steady State ◽  
Infusion Rate ◽  
Traditional Approach ◽  
Volume Of Distribution ◽  
Constant Volume ◽  
Constant Infusion ◽  
Steady State Condition ◽  
Fixed Volume ◽  
The One ◽  
Infusion Technique

The most common approach for estimating substrate rate of appearance (Ra) is use of the single-pool model first proposed by R. W. Steele, J. S. Wall, R. C. DeBodo, and N. Altszuler. ( Am. J. Physiol. 187: 15–24, 1956). To overcome the model error during highly non-steady-state conditions due to the assumption of a constant volume of distribution (V), two strategies have been proposed: 1) use of a variable tracer infusion rate to minimize tracer-to-tracee ratio (TTR) variations (fixed-volume approach) or 2) use of two tracers of the same substrate with one infused at a constant rate and the other at a variable rate (variable-volume approach or approach of T. Issekutz, R. Issekutz, and D. Elahi. Can. J. Physiol. Pharmacol. 52: 215–224, 1974). The goal of this study was to compare the results of these two strategies for the analysis of the kinetics of glycerol and glucose under the non-steady-state condition created by a constant infusion of epinephrine (50 ng ⋅ kg−1 ⋅ min−1) with the traditional approach of Steele et al., which uses a constant infusion and fixed volume. The results showed that for glucose and glycerol the estimates of Raobtained with the constant and the variable tracer infusion rate and the equation of Steele et al. were comparable. The variable tracer infusion approach was less sensitive to the choice of V in estimating Ra for glycerol and glucose, although the advantage of changing the tracer infusion rate was greater for glucose than for glycerol. The model of Issekutz et al. showed instability when the ratio TTR1/TTR2approaches a constant value, and the model is more sensitive to measurement error than the constant-volume model for glucose and glycerol. We conclude that the one-tracer constant-infusion technique is sufficient in most cases for glycerol, whereas the one-tracer variable-infusion technique is preferable for glucose. Reasonable values for glucose Ra can be obtained with the constant-infusion technique if V = 145 ml/kg.

Secretory dynamics of 1α-hydroxycorticosterone in the elasmobranch fish, Scyliorhinus canicula

1984 ◽  
Vol 103 (2) ◽  
pp. 205-211 ◽  
Author(s):  
N. Hazon ◽  
I. W. Henderson
Keyword(s):  
Sodium Chloride ◽  
Sea Water ◽  
Specific Activity ◽  
Plasma Concentrations ◽  
High Specific Activity ◽  
Constant Infusion ◽  
Metabolic Clearance ◽  
Plasma Osmolarity ◽  
Scyliorhinus Canicula ◽  
Infusion Technique

ABSTRACT Peripheral plasma concentrations, metabolic clearance rates (MCR) and blood production rates (BPR) of 1α-hydroxycorticosterone (1-OH-B) were determined in female dogfish (Scyliorhinus canicula) under varying environmental conditions. The constant-infusion technique, using high specific activity tritiated 1-OH-B, was applied to measure the MCR, and BPR were derived from the product of plasma concentration and MCR at equilibrium. Urea plasma clearances and apparent BPR were assessed in a similar manner. Fish were adapted stepwise to 140, 120, 90, 80, 70, 60 and 50% normal sea water (about 1000 mosmol/l). In all cases 1-OH-B was the major corticosteroid, cortisol and corticosterone were sought but never detected. In environments of reduced osmolarity, plasma osmolarity, sodium, chloride and urea concentrations all declined, alongside increases in plasma concentrations, MCR and BPR of 1-OH-B. In fish held in environments at concentrations greater than normal sea water, plasma osmolarity, sodium, chloride and urea concentrations all increased. Plasma clearance of urea increased in fish held in environments more dilute than sea water, while it decreased in the more hyperosmotic waters. It is tentatively concluded that homeostasis of plasma composition, with particular respect to urea, is in part regulated by 1-OH-B in the dogfish. J. Endocr. (1984) 103, 205–211

Changes in glycerol kinetics after E. coli endotoxin administration in dogs

1984 ◽  
Vol 246 (3) ◽  
pp. R325-R330
Author(s):  
O. P. McGuinness ◽  
J. J. Spitzer
Keyword(s):  
Steady State ◽  
Infusion Rate ◽  
Volume Of Distribution ◽  
Constant Infusion ◽  
Metabolic Clearance ◽  
Glycerol Concentration ◽  
Endotoxin Administration ◽  
E Coli ◽  
The Face ◽  
Anesthetized Dogs

The metabolic clearance rate (MCR) and maximal rate of glycerol removal (Rd max) were determined in anesthetized dogs at two time periods after the intravenous administration of either Escherichia coli endotoxin or saline. The nonisotopic method employed in these studies to determine the MCR of glycerol consisted of a constant infusion of glycerol at three different infusion rates. At each infusion rate a steady-state glycerol concentration was obtained. The reciprocal of the slope of the linear relationship between the glycerol infusion rate and the change in the steady-state arterial glycerol concentration was equal to the MCR of glycerol. Administration of endotoxin significantly decreased the MCR of glycerol, whereas the volume of distribution of glycerol was not altered significantly. The arterial glycerol turnover remained unaltered, whereas arterial glycerol concentration increased after endotoxin administration. The studies demonstrate that the elevated arterial glycerol concentration maintained the rate of glycerol turnover in the face of decreased efficiency of glycerol removal after endotoxin administration.

Δ5-androstenediol: kinetics of metabolism and binding to plasma proteins in normal post-menopausal women

1982 ◽  
Vol 99 (2) ◽  
pp. 309-313 ◽  
Author(s):  
Charles E. Bird ◽  
John Tremblay ◽  
Valerie Masters ◽  
Albert F. Clark
Keyword(s):  
Young Women ◽  
Plasma Proteins ◽  
Constant Infusion ◽  
Metabolic Clearance ◽  
Androgenic Activity ◽  
Menopausal Women ◽  
Post Menopausal ◽  
Infusion Technique ◽  
Kinetics Of ◽  
Free Plasma

Abstract. Δ5-androstenediol (Δ5-diol) while having minimal androgenic activity is of potential biological importance because it binds to oestrogen receptors and has oestrogenic activity in several systems. We have examined Δ5-diol metabolism in post-menopausal women utilizing the constant infusion technique. The metabolic clearance rate for 11 subjects was 763 ± 50 1/24 h or 467 ± 30 1/m2/24 h. Labelled dehydroepiandrosterone, testosterone, Δ4-androstenedione, androsterone and the sulphates of Δ5-diol, dehydroepiandrosterone and androsterone were found in the plasma. Of all the kinetic parameters only the conversion ratio for dehydroepiandrosterone sulphate was different from that for young women (4.958 ± 0.410 for young women vs 3.084 ± 0.220 for older women). The plasma concentration of Δ5-diol was 0.94 ± 0.19 ng/ml and the calculated blood production rate was 686 ± 80 μg/24 h. The per cent free plasma Δ5-diol was 4.6 ± 0.25. These values are slightly lower but not significantly different from those previously reported for normal young women.

Lactate metabolism in resting and exercising dogs

1976 ◽  
Vol 40 (3) ◽  
pp. 312-319 ◽  
Author(s):  
B. Issekutz ◽  
W. A. Shaw ◽  
A. C. Issekutz
Keyword(s):  
Constant Infusion ◽  
Metabolic Clearance ◽  
Turnover Rates ◽  
Lactate Turnover ◽  
Hepatic Glucose ◽  
Lactate Levels ◽  
Glucose Output ◽  
Infusion Technique ◽  
Linear Manner

The effect of treadmill run on the turnover rates of glucose ([2-3H]glucose) and lactate ([U-14C]lactate), on the rates of oxidation (ROX) of lactate, and its conversion to glucose (L LEADS TO G) were measured with the primed constant-infusion technique. Comparable lactate turnover rates were obtained at rest by infusing epinephrine, or Na-L(+)-lactate with or without norepinephrine. With increasing lactate levels (L) the rate of disappearance (RdL), ROX, and L leads to G increase in a linear manner. At the same lactate level, RdL, ROX, and L leads to G are significantly higher in the running dog. Exercise increased the metabolic clearance rate of lactate threefold. At rest ROX and L leads to G represented about 50% and 18–19% of RdL, respectively. The corresponding values in the running dogs were 55% and 25%, respectively. At rest about 9% of the hepatic glucose output arose from lactate while during exercise this varied from 7 to 26% depending on RdL. It is concluded that a) the working muscle produces and utilizes lactate at the same time, and b) “in vivo” the major factor which controls both ROX and gluconeogenesis is the substrate supply.

Antidiuretic effect of subnormal levels of arginine vasopressin in normal humans

1990 ◽  
Vol 259 (1) ◽  
pp. R53-R60 ◽  
Author(s):  
L. J. Andersen ◽  
J. L. Andersen ◽  
H. J. Schutten ◽  
J. Warberg ◽  
P. Bie
Keyword(s):  
Arginine Vasopressin ◽  
Free Water ◽  
Human Kidney ◽  
Urine Osmolality ◽  
Significant Rise ◽  
Constant Infusion ◽  
Free Water Clearance ◽  
Water Load ◽  
Normal Humans ◽  
Renal Responses

The renal responses to 120-min infusions of arginine vasopressin (AVP) were investigated in healthy volunteers undergoing water diuresis induced by an oral water load of 20 ml/kg body wt. AVP at 1 pg.min-1.kg-1 (approximately 10(-15) mol.min-1.kg-1) decreased urine flow (12.2 +/- 1.7 to 7.4 +/- 1.5 ml/min) and free water clearance (9.7 +/- 1.5 to 4.8 +/- 1.4 ml/min) and increased urine osmolality (Uosmol; 71 +/- 6 to 115 +/- 15 mosmol/kgH2O); 5 pg.min-1.kg-1 elicited pronounced antidiuresis (14.4 +/- 0.9 to 0.9 +/- 0.3 ml/min) with maximal Uosmol of 621 +/- 95 mosmol/kg. In response to 25 pg.min-1.kg-1, maximal Uosmol was 869 +/- 38 mosmol/kg. Responses developed gradually and stabilized within the 2nd h of infusion. AVP at 1 and 5 pg.min-1.kg-1 was without effect for at least 20 min. Only 25 pg.min-1.kg-1 caused a significant rise in plasma AVP (1.2 +/- 0.2-2.0 +/- 0.1 pg/ml), and with this dose sodium excretion decreased. The rates of K+ excretion, as well as plasma aldosterone and atrial natriuretic peptide concentrations, were unaffected by AVP. It is concluded that the human kidney is sensitive to changes in the rate of secretion of AVP of less than 1 pg.min-1.kg-1 and that the maximal change occurs after 1-2 h of constant infusion. It is estimated that the rate of infusion of AVP required to produce isosmolar urine during overhydration is approximately 3 pg.min-1.kg-1.

CRITICAL ANALYSIS OF METHODS FOR ESTIMATING PRODUCTION RATES OF FSH

1975 ◽  
Vol 80 (2) ◽  
pp. 275-283 ◽  
Author(s):  
Salvatore Raiti ◽  
Robert M. Blizzard ◽  
Robert Penny ◽  
Claude J. Migeon
Keyword(s):  
Urinary Excretion ◽  
Clearance Rate ◽  
Critical Analysis ◽  
Constant Infusion ◽  
Metabolic Clearance ◽  
Production Rates ◽  
Metabolic Clearance Rate ◽  
Normal Men ◽  
Infusion Technique ◽  
Normal Adults

ABSTRACT The urinary excretion method and the constant infusion technique were used to estimate hFSH production rates (PR) in three normal men (aged 25–40 years). Both studies were also done in a hypophysectomized nine year old boy. The PR of hFSH in the urinary excretion studies ranged from 20.0 to 45.7 IU/24 h, whereas the constant infusion studies yielded PR's of 68.7 to 107.8 IU/24 h. Possible reasons for the discrepancy of the results obtained by the two methods are discussed. In the hypophysectomized patient, the metabolic clearance rate (MCR) of infused hFSH was much lower (4.3 ml/min) than in the normal adults (7.8 to 12.0 ml/min) and was not affected by the dose of hFSH given.

EFFECTS OF ARGININE-, LYSINE- AND LEUCINE-VASOPRESSIN ON URINARY OSMOLALITY AND RATE OF URINE FLOW IN HYDRATED RATS AND DOGS

1959 ◽  
Vol XXXII (I) ◽  
pp. 134-141 ◽  
Author(s):  
Niels A. Thorn
Keyword(s):  
Arginine Vasopressin ◽  
Urine Osmolality ◽  
Urine Flow ◽  
The Other ◽  
Maximum Increase ◽  
Urinary Osmolality ◽  
Lysine Vasopressin

ABSTRACT Arginine-, lysine- and leucine-vasopressin, injected i. v. into hydrated rats or dogs caused different patterns of response in that urine osmolality fell much more slowly after the maximum increase following arginine-vasopressin, than after the other two preparations. Using 3 different parameters for antidiuretic response, arginine-vasopressin was somewhat more potent than leucine-vasopressin in both rats and dogs, considerably more potent than lysine-vasopressin in rats, and much more so in dogs.

scholarly journals Plasma membrane glycosphingolipid signaling: a turning point

2021 ◽  
Author(s):  
Elena Chiricozzi
Keyword(s):  
Plasma Membrane ◽  
Chemical Synthesis ◽  
Bioinformatic Analysis ◽  
Membrane Receptors ◽  
Outer Side ◽  
Neuronal Homeostasis ◽  
Extracellular Stimuli ◽  
Conceptual Shift ◽  
Plasma Membrane Receptors ◽  
Key Events

AbstractPlasma membrane interaction is highly recognized as an essential step to start the intracellular events in response to extracellular stimuli. The ways in which these interactions take place are less clear and detailed. Over the last decade my research has focused on developing the understanding of the glycosphingolipids-protein interaction that occurs at cell surface. By using chemical synthesis and biochemical approaches we have characterized some fundamental interactions that are key events both in the immune response and in the maintenance of neuronal homeostasis. In particular, for the first time it has been demonstrated that a glycolipid, present on the outer side of the membrane, the long-chain lactosylceramide, is able to directly modulate a cytosolic protein. But the real conceptual change was the demonstration that the GM1 oligosaccharide chain is able, alone, to replicate numerous functions of GM1 ganglioside and to directly interact with plasma membrane receptors by activating specific cellular signaling. In this conceptual shift, the development and application of multidisciplinary techniques in the field of biochemistry, from chemical synthesis to bioinformatic analysis, as well as discussions with several national and international colleagues have played a key role.

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