Age-dependent changes of cardiac neuronal noradrenaline reuptake transporter (uptake1) in the human heart
Kirsten Leineweber, PhD*,
Thekla Wangemann ,
Christine Giessler*,
Heike Bruck*,
Stefan Dhein, MD ,
Martin Kostelka, MD,
Friedrich-Wilhelm Mohr, MD,
Rolf-Edgar Silber, MD and
Otto-Erich Brodde, PhD*, ,*
* Institute of Pharmacology, Halle, Germany
Clinic for Cardiothoracic Surgery, Martin-Luther-University of Halle-Wittenberg, Halle, Germany
Heart Center, Clinic for Cardiac Surgery, Leipzig, Germany
Departments of Pathophysiology and Nephrology, University of Essen School of Medicine, Essen, Germany
View larger version (24K):
[in a new window]
|
Figure 1 (A) Concentration-dependent binding of (3H)-nisoxetine to membranes obtained from the right atria (RA) of 5 children and 2 young adults in group A (5 males and 2 females; mean age 14 ± 3 years) and 11 elderly patients in group B (8 males and 3 females; mean age 60 ± 3 years) (New York Heart Association functional class 1.73 ± 0.19). Ordinate: (3H)-nisoxetine concentration in fmol specifically bound/mg protein; abscissa: (3H)-nisoxetine concentration in nmol/l. Data are presented as the mean value ± SEM. ***p < 0.001 vs. group A. (B) Inhibition of specific (3H)-nisoxetine binding (2 nmol/l) to RA membranes obtained from 8 elderly patients (6 males and 2 females; mean age 67 ± 3 years) by uptake inhibitors. Ordinate: specific (3H)-nisoxetine binding as percent; abscissa: molar concentrations of uptake inhibitors. Data are presented as the mean value ± SEM of two experiments performed in triplicate with log (mol/l) IC50 values: desipramine –7.51 ± 0.20; nisoxetine –7.09 ± 0.06; cocaine –5.52 ± 0.08; and GBR 12909 –5.35 ± 0.10.
|
|
View larger version (19K):
[in a new window]
|
Figure 2 Correlation (solid line = linear regression) between right atrial (RA) neuronal noradrenaline transporter (NAT) density and age of 18 patients (see Fig. 1A). Ordinate: RA NAT density in fmol of (3H)-nisoxetine specifically bound/mg protein; abscissa: age of patients in years. Solid line: y = –1.104x + 177.4; r = –0.906; R2 = 0.644; p < 0.0001. Dotted lines represent 95% confidence limits for the regression line.
|
|
View larger version (15K):
[in a new window]
|
Figure 3 Specific (3H)-noradrenaline uptake1 in right atrial (RA) slices obtained from 4 children of group A (A) (2 males and 2 females; mean age 5 ± 2 years) and 5 elderly patients of group B (B) (5 males; mean age 59 ± 5 years) (New York Heart Association functional class 1.80 ± 0.20). Ordinate: specific (3H)-noradrenaline uptake1 (in the presence of 40 µmol/l corticosterone) in pmol (3H)-noradrenaline/mg tissue per 15 min; abscissa: (3H)-noradrenaline concentrations in nmol/l. Data are presented as the mean value ± SEM. **p < 0.01 and ***p < 0.001 vs. group A.
|
|
View larger version (18K):
[in a new window]
|
Figure 4 Effects of 1 µmol/l desipramine (DMI) on the positive inotropic effect of noradrenaline (in the presence of 1 µmol/l phentolamine) in right atrial (RA) trabecular strips obtained from 5 children in group A (A, left panel) (3 males and 2 females; mean age 9 ± 4 years) and from 7 elderly patients in group B (B, right panel) (5 males and 2 females; mean age 60 ± 3 years) (New York Heart Association functional class 1.71 ± 0.18). Ordinates: positive inotropic effect in percent maximal response; abscissa: molar concentrations of noradrenaline. The basal force of contraction was 2.5 ± 0.4 mN (without DMI) and 5.0 ± 0.8 mN (with DMI) in group A and 3.6 ± 0.6 mN (without DMI) and 4.2 ± 1.3 mN (with DMI) in group B. The maximal force of contraction was 7.2 ± 0.6 mN (without DMI) and 6.7 ± 1.0 mN (with DMI) in group A and 8.7 ± 0.7 mN (without DMI) and 6.1 ± 1.3 mN (with DMI) in group B. Data are presented as the mean value ± SEM.
|
|
|
