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Cyclic GMP protein kinase activity is reduced in thyroxine‐induced hypertrophic cardiac myocytes
Author(s) -
Yan Lin,
Zhang Qihang,
Scholz Peter M,
Weiss Harvey R
Publication year - 2003
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2003.03936.x
Subject(s) - medicine , myocyte , endocrinology , guanosine , protein kinase a , chemistry , kinase , biology , biochemistry
Summary 1. We tested the hypothesis that the cGMP‐dependent protein kinase has major negative functional effects in cardiac myocytes and that the importance of this pathway is reduced in thyroxine (T 4 ; 0.5 mg/kg per day for 16 days) hypertrophic myocytes. 2. Using isolated ventricular myocytes from control ( n = 7) and T 4 ‐treated ( n = 9) rabbit hypertrophic hearts, myocyte shortening was studied with a video edge detector. Oxygen consumption was measured using O 2 electrodes. Protein phosphorylation was measured autoradiographically. 3. Data were collected following treatment with: (i) 8‐(4‐chlorophenylthio)guanosine‐3′,5′‐monophosphate (PCPT; 10 −7 or 10 −5 mol/L); (ii) 8‐bromo‐cAMP (10 −5 mol/L) followed by PCPT; (iii) β‐phenyl‐1, N 2 ‐etheno‐8‐bromoguanosine‐3′,5′‐monophosphorothioate, SP‐isomer (SP; 10 −7 or 10 −5 mol/L); or (iv) 8‐bromo‐cAMP (10 −5 mol/L) followed by SP. 4. There were no significant differences between groups in baseline percentage shortening (Pcs; 4.9 ± 0.2 vs 5.6 ± 0.4% for control and T 4 groups, respectively) and maximal rate of shortening (Rs; 64.8 ± 5.9 vs 79.9 ± 7.1 µm/ s for control and T 4 groups, respectively). Both SP and PCPT decreased Pcs (−43 vs −21% for control and T 4 groups, respectively) and Rs (−36 vs −22% for control and T 4 groups, respectively), but the effect was significantly reduced in T 4 myocytes. 8‐Bromo‐cAMP similarly increased Pcs (28 vs 23% for control and T 4 groups, respectively) and Rs (20 vs 19% for control and T 4 groups, respectively). After 8‐bromo‐cAMP, SP and PCPT decreased Pcs (−34%) and Rs (−29%) less in the control group. However, the effects of these drugs were not altered in T 4 myocytes (Pcs −24%; Rs −22%). Both PCPT and cAMP phosphorylated the same five protein bands. In T 4 myocytes, these five bands were enhanced less. 5. We conclude that, in control ventricular myocytes, the cGMP‐dependent protein kinase exerted major negative functional effects but, in T 4 ‐induced hypertrophic myocytes, the importance of this pathway was reduced and the interaction between cAMP and the cGMP protein kinase was diminished.