Sites of adenosine production in cardiac and skeletal muscle

Rubio, Rafael; Berne, Robert M.; Dobson, James G.

doi:10.1152/ajplegacy.1973.225.4.938

Cited by 200 publications

(88 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Membrane-bound 5Ј-nucleotidase has been documented histochemically on the cell surface of cardiomyocytes and vascular cells of guinea pig heart. 16 In this species, AMP is recovered from an extracellular fluid region, 7 and coronary venous adenine nucleotide release is 40 pmol ⅐ min Ϫ1 ⅐ g Ϫ1 under control conditions and 430 pmol ⅐ min Ϫ1 ⅐ g Ϫ1 during ecto-5Ј-nucleotidase inhibition by ␣,␤-methyleneadenosine diphosphate. 8 This release is quantitatively sufficient to account for the extracellular adenosine production rate estimated in the present experiments.…”

Section: Extracellular Adenosine Productionmentioning

confidence: 90%

Quantification of Extracellular and Intracellular Adenosine Production

et al. 1999

View full text Add to dashboard Cite

Background-Inhibitors of adenosine membrane transport cause vasodilation and enhance the plasma adenosine concentration. However, it is unclear why the plasma adenosine concentration rises rather than falls when membrane transport is inhibited. We tested the hypothesis that the cytosolic adenosine concentration exceeds the interstitial concentration under well-oxygenated conditions. Methods and Results-In isolated, isovolumically working guinea pig hearts (nϭ50), the release rate of adenosine and accumulation of S-adenosylhomocysteine (after 20 minutes of 200 mol/L homocysteine), a measure of the free cytosolic adenosine concentration, were determined in the absence and presence of specific and powerful blockers of adenosine membrane transport (nitrobenzylthioinosine 1 mol/L), adenosine deaminase (erythro-9-hydroxy-nonyladenine 5 mol/L), and adenosine kinase (iodotubericidine 10 mol/L). Data analysis with a distributed multicompartment model revealed a total cardiac adenosine production rate of 2294 pmol ⅐ min Ϫ1 ⅐ g Ϫ1 , of which 8% was produced in the extracellular region. Because of a high rate of intracellular metabolism, however, 70.3% of extracellularly produced adenosine was taken up into cellular regions, an effect that was effectively eliminated by membrane transport block. The resulting Ϸ2.8-fold increase of the interstitial adenosine concentration evoked near-maximal coronary dilation. Conclusions-We rejected the hypothesis that the cytosolic adenosine concentration exceeds the interstitial. Rather, there is significant extracellular production, and the parenchymal cell represents a sink, not a source, for adenosine under well-oxygenated conditions. (Circulation. 1999;99:2041-2047.)

show abstract

Section: Extracellular Adenosine Productionmentioning

confidence: 90%

Quantification of Extracellular and Intracellular Adenosine Production

et al. 1999

View full text Add to dashboard Cite

show abstract

“…Two metabolic pathways are considered as potential sources of adenosine formation in mammalian tissues (Rubio et al, 1973;Schutz et al, 1981). The first, involving 5'-NT, yields adenosine through enzymatic dephosphorylation of AMP.…”

Section: '-Nt and Ada Are The Major Developmentally Regulated Purinementioning

confidence: 99%

“…AMP can also be degraded to IMP by the enzyme adenylate deaminase (AMP-DA) (Rubio et al, 1973;Barankiewicz et al, 1988). We assayed AMP-DA activity by measuring the conversion of AMP to IMP in the absence of M 8 + .…”

Section: '-Nt and Ada Are The Major Developmentally Regulated Purinementioning

confidence: 99%

Adenosine levels in the postimplantation mouse uterus: Quantitation by HPLC‐fluorometric detection and spatiotemporal regulation by 5′‐nucleotidase and adenosine deaminase

Blackburn

Gao

Airhart

et al. 1992

Developmental Dynamics

View full text Add to dashboard Cite

Extracellular adenosine has the potential to influence many aspects of target cell metabolism. The present study has determined the endogenous levels of adenosine in the pregnant mouse uterus and developing embryodecidual unit with respect to the expression of two key enzymes of adenosine metabolism, 5'-nucleotidase (5'-NT; EC 3.1.3.5) and adenosine deaminase (ADA; EC 3.5.4.4). To measure adenosine levels, nucleoside extracts were etheno-derivatized and quantitated by high-performance liquid chromatography-fluorescence detection (0.03 pmollmg protein sensitivity). Adenosine levels were determined to be 0.18 nmol/mg protein in the nonpregnant uterus; however, two statistically significant changes were identified in the pregnant uterus: (1) a periimplantation surge between day 3 (0.24 nmoVmg protein) and day 5 (0.59 nmoYmg protein) of gestation (plug day 0; implantation day 4); and (2) an early postimplantation decline between day 6 (0.54 nmollmg protein) and day 7 (0.10 nmollmg protein). The periimplantation adenosine surge coincided with uterine expression of 5'-NT, an enzyme which catalyzes the irreversible dephosphorylation of 5'-AMP to adenosine. 5'-NT expression was shown by Northern blot analysis to peak in the embryo-decidual unit on day 5 of gestation and then to decline through day 9; transcripts remained elevated in the placenta between day 9 and day 13 (the latest day examined in this study). By use of specific enzyme histochemistry, most 5'-NT activity was localized to the primary decidual :zone on day 5. This expression subsequently declined during regression of the primary decidua; however, 5'-NT appeared on giant trophoblast ((days 7-13) and the metrial gland (days 11-13).Other purine catabolic enzymes degrading AMP (adenylate deaminase) or generating adenosine (S-adenosylhomocysteine hydrolase) were not detected in the embryo-decidual unit suggesting that the net flux of utero-placental AMP catabolism proceeds with adenosine as an intermediate, this being the major pathway of adenosine formation.The sharp drop in adenosine levels between day 6 and day 7 coincided with a rise in the activity and mRNA expression of ADA, an enzyme which catalyzes the irreversible deamination of adenosine to inosine. ADA was previously localized to the secondary decidual zone (days 6 1 l), secondary giant cells (days 7-13), and spongiotrophoblasts (days 8-13) in the mouse (Knudsen et al., 1991). Results of developmental Northern blot analysis demonstrated a direct correlation of relative 5'-NT/ADA mRNA band intensity to adenosine content between day 4 and day 9 of gestation, suggesting that the local availability of adenosine in the antimesometrium is dependent upon the distribution of these enzymatic activities. Purine nucleoside phosphorylase and xanthine oxidase, which are two catabolic enzymes acting subsequent to 5'-NT and ADA in the sequential degradation of AMP to xanthine, remained low and constant in the tissues examined suggesting that the catabolic pathway is geared toward regulation of adenosine le...

show abstract

“…We used multiple regression techniques (18,19) Chemical and mechanical factors within contracting muscle are thought to have -a profound effect in the hyperemia of exercise. Metabolic and electrolyte changes are important in limb muscles (20,21), but we have no data concerning the effect of these metabolites in the diaphragm.…”

Section: Introductionmentioning

confidence: 99%

“…METHODS Animal preparation. These studies were performed in 21 adult mongrel dogs which weighed [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] kg. The animals were initially anesthetized with pentobarbital, 25 mg/kg in- (6).…”

Section: Introductionmentioning

confidence: 99%

Diaphragmatic blood flow and energy expenditure in the dog. Effects of inspiratory airflow resistance and hypercapnia.

Rochester¹,

Bettini²

1976

J. Clin. Invest.

101

View full text Add to dashboard Cite

A B S T R A C T To investigate the mechanisms which enable the diaphragm to preserve ventilation when the work of breathing is elevated, we measured diaphragmatic blood flow (0 di) and oxygen consumption (Vo2 di) in lightly anesthetized dogs. The animals were studied when they breathed quietly, when they inhaled 5% CO2 in 21% or 14% 02, or when they inhaled these gas mixtures through moderate to severe inspiratory resistances. Q di was determined from the integrated diaphragmatic arteriovenous difference of krypton-85, by the Kety-Schmidt technique. V02 di was calculated as the product of Q di and the diaphragmatic arteriovenous oxygen difference ([A-Vy02 di). Alteration in these parameters consequent to augmentation of ventilatory effort were compared with concomitant alterations in diaphragmatic electrical activity (EMG di) and an inspiratory pleural pressure-time index (PPTI).Addition of inspiratory resistances combined with inhalation of CO2 usually increased Q di and consistently increased V02 di, EMG di, and PPTI, the maximum increases being approximately 400-1,600% above control levels. In individual animals, as inspiratory resistance was increased, V0o, di, EMG di, and PPTI rose in direct proportion to each other.In the group as a whole, during resistance breathing the oxygen requirements of the diaphragm were met by a combination of increased [A-Vy02 di and Q di. Unlike other skeletal muscles, oxygen extraction tended to plateau at peak loads, whereas blood flow continued to rise as PPTI and Vo2 di increased. We conclude that augmentation of perfusion permits the diaphragm to sustain high levels of contractile effort when the work of breathing is increased.

show abstract

Sites of adenosine production in cardiac and skeletal muscle

Cited by 200 publications

References 0 publications

Quantification of Extracellular and Intracellular Adenosine Production

Quantification of Extracellular and Intracellular Adenosine Production

Adenosine levels in the postimplantation mouse uterus: Quantitation by HPLC‐fluorometric detection and spatiotemporal regulation by 5′‐nucleotidase and adenosine deaminase

Diaphragmatic blood flow and energy expenditure in the dog. Effects of inspiratory airflow resistance and hypercapnia.

Contact Info

Product

Resources

About