Diadenosine tetraphosphate stimulates atrial ANP release via A(1) receptor: involvement of K(ATP) channel and PKC.
Diadenosine polyphosphates (APnAs) are endogenous compounds and exert diverse cardiovascular functions. However, the effects of APnAs on atrial ANP release and contractility have not been studied. In this study, the effects of diadenosine tetraphosphate (AP4A) on atrial ANP release and contractility, and their mechanisms were studied using isolated perfused rat atria. Treatment of atria with AP4A resulted in decreases in atrial contractility and extracellular fluid (ECF) translocation whereas ANP secretion and cAMP levels in perfusate were increased in a dose-dependent manner. These effects of AP4A were attenuated by A(1) receptor antagonist but not by A(2A) or A(3) receptor antagonist. Other purinoceptor antagonists also did not show any effects on AP4A-induced ANF release and contractility. The increment of ANP release and negative inotropy induced by AP4A was similar to those induced by AP3A, AP5A, and AP6A. Protein kinase A inhibitors accentuated AP4A-induced ANP secretion. In contrast, an inhibitor of phospholipase C, protein kinase C or sarcolemma K(ATP) channel completely blocked AP4A-induced ANP secretion. However, an inhibitor of adenylyl cyclase or mitochondria K(ATP) channel had no significant modification of AP4A effects. These results suggest that AP4A regulates atrial inotropy and ANP release mainly through A(1) receptor signaling involving phospholipase C-protein kinase C and sarcolemmal K(ATP) channel and that protein kinase A negatively modulates the effects of AP4A.
Yuan
Kuichang
K
Department of Physiology, Medical School, Center for Healthcare Technology Development, Chonbuk National University, Jeonju, Republic of Korea.
Cao
Chunhua
C
Bai
Guang Yi
GY
Kim
Sung Zoo
SZ
Kim
Suhn Hee
SH
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D006325:Heart Atria / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology; D015221:Potassium Channels / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D015398:Signal Transduction
D015226:Dinucleoside Phosphates; D015221:Potassium Channels; D020033:Protein Isoforms; D043682:Receptor, Adenosine A1; C117780:mitochondrial K(ATP) channel; C020733:diadenosine tetraphosphate; D009320:Atrial Natriuretic Factor; D011493:Protein Kinase C