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New Cardiology Study Findings Have Been Reported from West Virginia University (PP2 Prevents beta-Adrenergic Stimulation of Cardiac Pacemaker...

July 16, 2014

New Cardiology Study Findings Have Been Reported from West Virginia University (PP2 Prevents beta-Adrenergic Stimulation of Cardiac Pacemaker Activity)

By a News Reporter-Staff News Editor at Biotech Week -- Researchers detail new data in Cardiology. According to news reporting from Morgantown, West Virginia, by NewsRx journalists, research stated, "One of the main strategies for cancer therapy is to use tyrosine kinase inhibitors for inhibiting tumor proliferation. Increasing evidence has demonstrated the potential risks of cardiac arrhythmias (such as prolonged QT interval) of these drugs."

The news correspondents obtained a quote from the research from West Virginia University, "We report here that a widely used selective inhibitor of Src tyrosine kinases, 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo[3,4-d] pyrimidine (PP2), can inhibit and prevent beta-adrenergic stimulation of cardiac pacemaker activity. First, in dissected rat sinus node, PP2 inhibited and prevented the isoproterenol-induced increase of spontaneous beating rate. Second, in isolated rat sinus node myocytes, PP2 suppressed the hyperpolarization-activated 'funny' current (traditionally called cardiac pacemaker current, If) by negatively shifting the activation curve and decelerating activation kinetics. Third, in isolated rat sinus node myocytes, PP2 decreased the Src kinase activity, the cell surface expression, and tyrosine phosphorylation of hyperpolarization-activated, cyclic nucleotide-modulated channel 4 (HCN4) channel proteins. Finally, in human embryonic kidney 293 cells overexpressing recombinant human HCN4 channels, PP2 reversed the enhancement of HCN4 channels by isoproterenol and inhibited 573x, a cyclic adeno-sine momophosphate-insensitive human HCN4 mutant. These results demonstrated that inhibition of Src kinase activity in heart by PP2 decreased and prevented b-adrenergic stimulation of cardiac pacemaker activity."

According to the news reporters, the research concluded: "These effects are mediated, at least partially, by a cAMP-independent attenuation of channel activity and cell surface expression of HCN4, the main channel protein that controls the heart rate."

For more information on this research see: PP2 Prevents beta-Adrenergic Stimulation of Cardiac Pacemaker Activity. Journal of Cardiovascular Pharmacology, 2014;63(6):533-543. Journal of Cardiovascular Pharmacology can be contacted at: Lippincott Williams & Wilkins, 530 Walnut St, Philadelphia, PA 19106-3621, USA. (Lippincott Williams and Wilkins -; Journal of Cardiovascular Pharmacology -

Our news journalists report that additional information may be obtained by contacting J.Y. Huang, West Virginia University, Heart Inst Hlth Sci Center, Morgantown, WV 26506, United States. Additional authors for this research include Y.C. Lin, S. Hileman, K.H. Martin, R. Hull and H.G. Yu (see also Cardiology).

Keywords for this news article include: Kinase, Tyrosine, Morgantown, Cardiology, West Virginia, United States, Aromatic Amino Acids, Enzymes and Coenzymes, North and Central America

Our reports deliver fact-based news of research and discoveries from around the world. Copyright 2014, NewsRx LLC

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Source: Biotech Week

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