Interaction between cyclic GMP protein kinase and cyclic AMP may be diminished in stunned cardiac myocytes

Lin Yan, Kepal N. Patel, Qihang Zhang, Peter M. Scholz, Harvey R. Weiss

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

We tested the hypothesis that the importance of the negative functional effects of the cyclic GMP protein kinase would be reduced in stunned (simulated ischemia/reperfusion) cardiac myocytes. Ventricular cardiac myocytes were isolated from New Zealand white rabbits (N = 7). Myocytes were studied at baseline and after simulated ischemia (15 min of 95% N2-5% CO2 at 37 °C) followed by simulated reperfusion (reoxygenation). Cell shortening was studied with a video edge detector; O2 consumption was measured using O2 electrodes. Protein phosphorylation was measured autoradiographically after gel electrophoresis. Functional and metabolic data were acquired after: (1) 8-(4-chlorophenylthio)guanosine-3′,5′-monophosphate (PCPT, cGMP protein kinase agonist) 10-7 or 10-5 M; (2) 8-Br-cAMP 10-5 M followed by PCPT 10-7 or 10-5 M; (3) β-phenyl-1, N2-etheno-8-bromoguanosine-3′,5′-monophosphorothioate, SP-isomer (SP, cGMP protein kinase agonist) 10-7 or 10-5 M; (2) 8-Br-cAMP 10-5 M followed by SP 10-7 or 10-5 M. At baseline, percent of shortening (Pcs) and maximal rate of shortening (Rs) were significantly lower in the stunned myocytes (Pcs: 5.0 ± 0.2% control vs. 3.8 ± 0.3 stunned; Rs: 64.8 ± 5.9 μm/s control vs. 46.9 ± 4.8 stunned). In both groups, PCPT and SP dose-dependently decreased Pcs and Rs. The effects were slightly, but not significantly, less in stunned myocytes. 8-Br-cyclic AMP significantly increased function in control, but not stunned myocytes (Pcs, 4.5 ± 0.5 to 6.2 ± 0.8 control vs. 3.1 ± 0.2 to 3.6 ± 0.2 stunned). The negative functional effects of PCPT and SP were diminished after 8-Br-cyclic AMP in control (from -39% to-29%) and diminished significantly more in the stunned myocytes (-19%). PCPT and cyclic AMP phosphorylated similar protein bands. In stunned myocytes, three (22, 31 and 53 kDa) bands were enhanced less by PCPT.

Original languageEnglish (US)
Pages (from-to)11-19
Number of pages9
JournalEuropean Journal of Pharmacology
Volume426
Issue number1-2
DOIs
StatePublished - Aug 24 2001

All Science Journal Classification (ASJC) codes

  • Pharmacology

Keywords

  • CGMP protein kinase
  • Ischemia/reperfusion
  • Rabbit
  • cAMP
  • cGMP

Fingerprint

Dive into the research topics of 'Interaction between cyclic GMP protein kinase and cyclic AMP may be diminished in stunned cardiac myocytes'. Together they form a unique fingerprint.

Cite this