TY - JOUR
T1 - Diadenosine 5',5-P1,P5-pentaphosphate harbors the properties of a signaling molecule in the heart
AU - Jovanovic, Aleksandar
AU - Jovanovic, Sofija
AU - Mays, Dennis C.
AU - Lipsky, James J.
AU - Terzic, Andre
N1 - Funding Information:
We thank Ms. Janet Pike for her valuable technical assistance. This research was supported by a Merck Sharp & Dohme International Award in Clinical Pharmacology, and grants from the American Heart Association, the Miami Heart Research Institute, the Bruce and Ruth Rappaport Program in Vascular Biology and Gene Delivery, the John Tainsh Heart Research Fund, and by the U.S. Department of Health and Human Services (FDT-000-886).
PY - 1998/2/27
Y1 - 1998/2/27
N2 - Dinucleotide polyphosphates (ApnA) have emerged as signaling molecules in rapidly dividing cells. The presence and role of Ap5A in the heart remain unknown. Here, we report that the myocardium contains abundant amounts of diadenosine 5',5-(P)1,P5-pentaphosphate (Ap5A), a member of the ApnA family. Ischemia induced 10-fold decrease in the myocardial concentration of Ap5A. A target of Ap5A action was identified to be the cardiac ATP-sensitive K+ (K(ATP)) channel, a metabolismsensitive ion conductance activated in ischemia. At levels found in hearts prior to ischemia, Ap5A maintained a low probability of KATe channel opening, but at levels found in hearts following ischemia, Ap5A allowed a high probability of K(ATP) channel opening. Taken together, the present data suggest that Ap5A harbors the properties of a signaling molecule involved in the cardiac response to metabolic stress.
AB - Dinucleotide polyphosphates (ApnA) have emerged as signaling molecules in rapidly dividing cells. The presence and role of Ap5A in the heart remain unknown. Here, we report that the myocardium contains abundant amounts of diadenosine 5',5-(P)1,P5-pentaphosphate (Ap5A), a member of the ApnA family. Ischemia induced 10-fold decrease in the myocardial concentration of Ap5A. A target of Ap5A action was identified to be the cardiac ATP-sensitive K+ (K(ATP)) channel, a metabolismsensitive ion conductance activated in ischemia. At levels found in hearts prior to ischemia, Ap5A maintained a low probability of KATe channel opening, but at levels found in hearts following ischemia, Ap5A allowed a high probability of K(ATP) channel opening. Taken together, the present data suggest that Ap5A harbors the properties of a signaling molecule involved in the cardiac response to metabolic stress.
KW - Diadenosine pentaphosphate
KW - Diadenosine polyphosphate
KW - Heart
KW - Ischemia
KW - K(ATP) channel
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U2 - 10.1016/S0014-5793(98)00114-8
DO - 10.1016/S0014-5793(98)00114-8
M3 - Article
C2 - 9515730
AN - SCOPUS:0032570648
SN - 0014-5793
VL - 423
SP - 314
EP - 318
JO - FEBS Letters
JF - FEBS Letters
IS - 3
ER -