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- Title
Hypertrophic responsiveness of cardiomyocytes to α- or β-adrenoceptor stimulation requires sodium-proton-exchanger-1 (NHE-1) activation but not cellular alkalization
- Authors
Schäfer, Matthias; Schäfer, Claudia; Michael Piper, Hans; Schlüter, Klaus-Dieter
- Abstract
The influence of the sodium-proton-exchanger-1 (NHE-1) inhibitor HOE694 on α- or β-adrenoceptor mediated stimulation of protein synthesis was investigated in cultured ventricular cardiomyocytes from adult rat pre-treated with fetal calf serum to induce hypertrophic responsiveness to β-adrenoceptor stimulation. Stimulation of α-adrenoceptors with phenylephrine (10 μM) in bicarbonate-free medium caused cellular alkalization (ΔpHi: +0.17±0.02, n=5, P<0.05). HOE694, an NHE-1 inhibitor, completely abolished this effect. [14C]phenylalanine incorporation into cellular protein mass increased in the presence of phenylephrine by 23±8%, and this effect was also abolished in the presence of HOE694. HOE694 (1 μM) neither influenced basal protein synthesis nor interfered with α-adrenoceptor mediated activation of ERK2. Phorbol myristate acetate, a direct stimulator of protein kinase C, mimicked the effect of α-adrenoceptor stimulation in regard to protein synthesis, but did not lead to cellular alkalization. Protein synthesis increased in the presence of isoprenaline, a β-adrenoceptor agonist also. Again, HOE694 attenuated the stimulation of protein synthesis although isoprenaline did not cause cellular alkalization. In conclusion, the growth response to different hypertrophic stimuli, namely α- or β-adrenoceptor stimulation, is attenuated in the presence of the NHE-1 inhibitor HOE694 and this inhibition is independent from cellular alkalization.
- Subjects
HEART cells; ADRENERGIC receptors; CARDIAC hypertrophy
- Publication
European Journal of Heart Failure, 2002, Vol 4, Issue 3, p249
- ISSN
1388-9842
- Publication type
Article