A positive inotropic effect of ATP in the human cardiac atrium.
We studied contractile effects in isolated electrically driven (1 Hz) atrial preparations from patients undergoing cardiac bypass surgery. ATP concentration dependently (10, 30, and 100 microM) and rapidly decreased force of contraction (negative inotropic effect, NIE) and thereafter more slowly increased force of contraction. The maximum positive inotropic effect (PIE) at 100 microM ATP amounted to 152% of the predrug value (n = 9) and was stable and could be washed out fast and completely. The PIE did not affect time parameters of contraction (time to peak tension and time of relaxation). Moreover, a similar NIE and PIE were noted with adenosine 5'-O-(2-thiotriphosphate) (100 microM). In contrast 2-methyl-thio-ATP did not exert a NIE but only a PIE. In a second set of experiments, preparations were first incubated for 30 min with purinoreceptor antagonists and, in their continuous presence, 100 microM ATP was applied. However, the PIE and NIE of ATP could neither be blocked with suramin (100 and 500 microM), pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (50 microM), nor reactive blue 2 (30, 100, and 500 microM), which are known blockers for subtypes of P(2) receptors, or 1,3-dipropyl-cyclopentvl-xanthine (1 and 10 microM), a subtype (A(1) adenosine) P(1) receptor blocker. Likewise, the inhibitor of phospholipase C (PLC) activity (U-73122) and the inhibitor of adenylate cyclase activity (SQ-022563) (10 microM each) failed to affect the NIE and the PIE of ATP. We tentatively suggest that the PIE of ATP might be mediated via P(2X4)-like receptors. In summary, we describe a novel biphasic effect of ATP on force contraction in the isolated human atrium. It is conceivable that ATP plays a physiological role in the human heart, for instance, after cardiac injury to sustain contractility.
Gergs
Ulrich
U
Institut für Pharmakologie und Toxikologie, Medizinische Fakultät, Martin-Luther-Universität Halle-Wittenberg, Magdeburger Str. 4, D-06112 Halle, Germany.
Boknik
Peter
P
Schmitz
Wilhelm
W
Simm
Andreas
A
Silber
Rolf-Edgar
RE
Neumann
Joachim
J
D058916:Adenosine A1 Receptor Antagonists; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D002316:Cardiotonic Agents / Q000378:metabolism* / Q000494:pharmacology; D001026:Coronary Artery Bypass; D003327:Coronary Disease / Q000378:metabolism* / Q000601:surgery; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D006325:Heart Atria / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D058848:Receptors, Purinergic P2X4; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000187:drug effects; D013498:Suramin / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D014227:Triazines / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism; D014970:Xanthines / Q000494:pharmacology
D058916:Adenosine A1 Receptor Antagonists; D000067956:Adenylyl Cyclase Inhibitors; D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; D004963:Estrenes; C548226:P2RX4 protein, human; D058919:Purinergic P2 Receptor Antagonists; D011760:Pyrrolidinones; D043682:Receptor, Adenosine A1; D018048:Receptors, Purinergic P2; D058848:Receptors, Purinergic P2X4; D013873:Thionucleotides; D014227:Triazines; D014970:Xanthines; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; C012842:Cibacron Blue F 3GA; D011732:Pyridoxal Phosphate; D013498:Suramin; C022570:adenosine 5'-O-(2-thiotriphosphate); D000255:Adenosine Triphosphate; C051360:1,3-dipropyl-8-cyclopentylxanthine; D010738:Type C Phospholipases; D000262:Adenylyl Cyclases; C008501:2-methylthio-ATP