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A Nørgaard

Publications and source records attributed to A Nørgaard.

66 records · Page 4Linked to original sources
PubMed1984

Effect of thyroid function on number of Na-K pumps in human skeletal muscle.

To evaluate the effect of thyroid function on the number of Na-K pumps in skeletal muscle, the number of 3H-ouabain binding sites was measured in biopsy specimens from the vastus lateralis muscle of euthyroid subjects and patients with hypothyroidism or hyperthyroidism. In hypothyroidism there was a decrease of 50% in 3H-ouabain binding sites, and in hyperthyroidism there was an increase of 68% in 3H-ouabain binding sites. When thyroid status became normal after treatment the number of 3H-ouabain binding sites also became normal. There were significant correlations between several thyroid function tests and the number of 3H-ouabain binding sites. Free T4-index gave the highest r value (0.87). These changes may account for the variations in digitalis sensitivity associated with thyroid disorders.

Adult↗
PubMed1984

(Na+ + K+)-ATPase activity of crude homogenates of rat skeletal muscle as estimated from their K+-dependent 3-O-methylfluorescein phosphatase activity.

A highly sensitive fluorimetric assay using 3-O-methylfluorescein phosphate as substrate was used in the determination of K+-dependent phosphatase activity in preparations of rat skeletal muscle. The gastrocnemius muscle was chosen because of mixed fibre composition. Crude, detergent treated homogenate was used so as to avoid loss of activity during purification. K+-dependent phosphatase activities in the range 0.19-0.37 mumol X (g wet weight)-1 X min-1 were obtained, the value decreasing with age and K+-deficiency. Complete inhibition of the K+-dependent phosphatase was obtained with 10(-3) M ouabain. Using a KSCN-extracted muscle enzyme the intimate relation between K+-dependent phosphatase activity and (Na+ + K+)-activated ATP hydrolysis could be demonstrated. A molecular activity of 620 min-1 was estimated from simultaneous determination of K+-dependent phosphatase activity and [3H]ouabain binding capacity using the partially purified enzyme preparation. The corresponding enzyme concentration in the crude homogenates was calculated and corresponded well with the number of [3H]ouabain binding sites measured in intact muscles or biopsies hereof.

Animals↗
PubMed1984

Effect of K-depletion on 3H-ouabain binding and Na-K-contents in mammalian skeletal muscle.

K-depletion induced by K-deficient fodder led to hypokalemia, decreased K-content and increased Na-content in skeletal muscle of rats. The heart showed similar, although more modest changes, whereas brain, erythrocytes and liver maintained virtually constant Na-K-contents. K-depletion decreased total binding capacity for 3H-ouabain by up to 76%, an effect which could be demonstrated both in vitro and in vivo. Following 3 weeks of K-depletion, the apparent KD for 3H-ouabain binding to rat soleus was 1.3 X 10(-7) M as compared to 2.4 X 10(-7) M in controls. Also in mice and guinea pigs, K-depletion induced a selective loss of K from muscle and decreased 3H-ouabain binding capacity. K-depletion induced by diuretics or fluorohydrocortisone gave similar effects. The effects of K-depletion on 3H-ouabain binding capacity were confirmed by measurements of 3-O-methylfluorescein phosphatase activity, an enzyme activity which is closely correlated to the Na-K-ATPase activity. Following readministration of K, the K-contents of plasma and muscle reached control levels in 24 hours, but 3H-ouabain binding capacity was not normalized until after 6 days of K-repletion. In mammalian skeletal muscle, K-depletion leads to a marked and reversible reduction in 3H-ouabain binding capacity, which may be secondary to the selective loss of K or gain of Na.

Animals↗
PubMed1984

A method for the determination of the total number of 3H-ouabain binding sites in biopsies of human skeletal muscle.

A new method based on vanadate facilitated binding of 3H-ouabain has been applied for the quantitative determination of the number of 3H-ouabain binding sites (Na-K-pumps) in needle biopsies of human skeletal muscle. Samples of the vastus lateralis muscle weighing 2-8 mg showed specific and saturable binding of 3H-ouabain with an apparent KD of 1.9 X 10(-8) mol/l. In 20 healthy human subjects in the age range 25-80 years, the number of 3H-ouabain binding sites was 278 +/- 15 pmol/g wet weight with no relation to age or sex. In samples of the intercostal and rectus abdominis muscles, the number of 3H-ouabain binding sites varied from 225 to 280 pmol/g wet weight. These values are at least 2 times higher than those previously reported for human skeletal muscle. The number of 3H-ouabain and 3H-digoxin binding sites were identical, and ouabain (10(-3) mol/l) completely displaced specifically bound 3H-digoxin. When biopsies were frozen in liquid N2 immediately after withdrawal, storage at -20 degrees C for up to 11 weeks caused no significant change in the number of 3H-ouabain binding sites. The method allows quantitative determination of the number of 3H-ouabain binding sites in standard biopsies of human skeletal muscle to be performed by simple procedures within a few hours. This can be used for the study of conditions where the number of Na-K-pumps is known to undergo fluctuations.

Adult↗
PubMed1983

Effects of denervation on sodium, potassium and [3H]ouabain binding in muscles of normal and potassium-depleted rats.

K depletion leads to a selective loss of K from skeletal muscles, which is associated with a decrease in the number of [3H]ouabain binding sites. The significance of the nerve supply for these changes has been assessed in denervation experiments with K-depleted rats. In K-depleted rats (age 4-12 weeks) denervation led to a partial recovery of the K contents in soleus (46-77%), gastrocnemius (23%) and extensor digitorum longus (e.d.l.) muscles (19%) within 24 h. These effects were not prevented by beta-adrenoceptor blockade or mimicked by alpha-adrenoceptor blockade. In K-depleted rats the number of [3H]ouabain binding sites was not increased following denervation. In K-depleted rats 24 h of plaster immobilization of the entire hind limb caused 51% recovery of the total K content in soleus, whereas gastrocnemius and e.d.l. showed 49 and 16% recovery, respectively. Tenotomy for 3 h caused a rise in total K content of 33% in soleus muscles from K-depleted rats. Anaesthesia for 3 h increased the total K content by 23%. The recovery of K induced by denervation, immobilization in plaster, tenotomy or anaesthesia was associated with an equivalent decrease in Na content. Denervation performed before K depletion reduced the loss of K from soleus, but not from gastrocnemius and e.d.l. In both soleus and e.d.l. the number of [3H]ouabain binding sites, however, decreased to the same level as in the contralateral innervated muscles. Denervation reduced, but did not prevent, the increase in the number of [3H]ouabain binding sites seen after re-administration of K to K-depleted rats. It is concluded that the changes in Na-K contents seen after denervation in K-depleted rats are the outcome of cessation of muscle activity. The results give no support to the idea that the effects of K depletion on the K content and the number of [3H]ouabain binding sites in skeletal muscle are mediated by the peripheral nerves.

Animals↗
PubMed1982

Age-dependent changes in the number of [3H]ouabain-binding sites in rat soleus muscle.

The influence of age on the number of (Na+K+)-ATPase units in skeletal muscle has been assessed by measurements of [3H]ouabain binding in vitro and in vivo to rat soleus muscle. In vitro measurements showed that from the 2nd to the 28th day of life, the number of [3H]ouabain-binding sites increases from 120 to 580 pmol/g wet wt. This is followed by a decrease, until a plateau between 150 and 200 pmol/g is reached around 150 days after birth. 60 min after intraperitoneal injection of [3H]ouabain (12.5 mumol/kg body weight), the soleus muscles of 28-day-old rats had accumulated 2.4-times more 3H-activity per g wet wt. than muscles of 85-day-old rats and the 3H-activity in plasma was 54% lower. The results may explain the low sensitivity to digitalis glycosides found in infants as compared to premature or adult individuals.

Aging↗
PubMed1982

Effect of age, potassium depletion and denervation on specific displaceable [3H]ouabain binding in rat skeletal muscle in vivo.

1. Following intraperitoneal injection of [(3)H]ouabain in rats, the isotope is rapidly distributed in blood plasma available for binding to the Na-K-ATPase in the plasma membranes of most tissues. In skeletal muscle tissue excised and washed 4 x 30 min in ice-cold buffer, 95% of the (3)H activity retained was shown to be [(3)H]ouabain using a specific binding assay.2. The [(3)H]ouabain bound to soleus and extensor digitorum longus (e.d.l.) muscles in vivo and retained following wash-out in the cold showed the same saturation characteristics as those determined when binding took place in vitro.3. In soleus and e.d.l. muscles obtained from 28-day-old rats, the number of [(3)H]ouabain binding sites measured in vivo was 583+/-19 and 720+/-22 pmol/g wet wt., respectively, i.e. in good agreement with previous and present results obtained in vitro.4. In vivo measurements showed that 7 days after denervation, the number of [(3)H]ouabain binding sites in soleus and e.d.l. muscles was reduced by 22 and 13%, respectively.5. In the age interval from 28 to 85 days, the number of [(3)H]ouabain binding sites in soleus was found to decrease by 58%. Following I.P. injection of [(3)H]ouabain, the 85-day-old rats showed a more pronounced and sustained rise in plasma (3)H activity, which in part can be due to the reduced capacity for [(3)H]ouabain binding in skeletal muscle.6. K depletion induced by the administration of K-deficient diet for 3 weeks reduced [(3)H]ouabain binding by 63% in soleus muscles. In the K-depleted animals, the plasma (3)H activity measured 15 min after I.P. injection of [(3)H]ouabain was 77% higher than in controls receiving the same dose per kg body weight.7. The present in vivo results provide further support for the idea that increased digitalis toxicity due to increasing age or K depletion is related to reduced binding capacity for digitalis glycosides in skeletal muscle.

Aging↗
PubMedDate not supplied

Ouabain binding and Na+ content in resistance vessels and skeletal muscles of spontaneously hypertensive rats and K+-depleted rats.

The possible role of Na+ in the development of hypertension in rats was explored in measurements of intracellular Na+, 22Na efflux, and 3H-ouabain binding sites in resistance vessels and skeletal muscles. In resistance vessels obtained from 13-week-old spontaneously hypertensive rats (SHR) or age-matched Wistar-Kyoto rats (WKY), (Na)i, total or ouabain-resistant 22Na efflux, and the concentration of 3H-ouabain binding sites showed no significant differences. Soleus muscles obtained from 6-week-old and 13-week-old SHR contained 5 to 11% more 3H-ouabain binding sites than those of WKY. The small difference in ouabain binding probably was related more to variations in growth rate and strain than to the hypertension. In SHR and WKY the Na+ and K+ contents of gastrocnemius muscles were almost identical at 6 and 13 weeks of age. By contrast, in Wistar rats in which the (Na)i of skeletal muscle was increased sixfold by K+ depletion, the systolic blood pressure was decreased by 10%. The K+ depletion was associated with a 35 to 55% decrease in the concentration of 3H-ouabain binding sites in both resistance vessels and skeletal muscles. The results provide no support for any simple cause-effect relationships between either elevated (Na)i or altered concentration of 3H-ouabain binding sites and hypertension in SHR.

Animals↗