Adenosine 5'-triphosphate: a P2-purinergic agonist in the myocardium.
ATP, besides an intracellular energy source, is an agonist when applied to a variety of different cells including cardiomyocytes. Sources of ATP in the extracellular milieu are multiple. Extracellular ATP is rapidly degraded by ectonucleotidases. Today ionotropic P2X(1--7) receptors and metabotropic P2Y(1,2,4,6,11) receptors have been cloned and their mRNA found in cardiomyocytes. On a single cardiomyocyte, micromolar ATP induces nonspecific cationic and Cl(-) currents that depolarize the cells. ATP both increases directly via a G(s) protein and decreases Ca(2+) current. ATP activates the inward-rectifying currents (ACh- and ATP-activated K(+) currents) and outward K(+) currents. P2-purinergic stimulation increases cAMP by activating adenylyl cyclase isoform V. It also involves tyrosine kinases to activate phospholipase C-gamma to produce inositol 1,4,5-trisphosphate and Cl(-)/HCO(3)(-) exchange to induce a large transient acidosis. No clear correlation is presently possible between an effect and the activation of a given P2-receptor subtype in cardiomyocytes. ATP itself is generally a positive inotropic agent. Upon rapid application to cells, ATP induces various forms of arrhythmia. At the tissue level, arrhythmia could be due to slowing of electrical spread after both Na(+) current decrease and cell-to-cell uncoupling as well as cell depolarization and Ca(2+) current increase. In as much as the information is available, this review also reports analog effects of UTP and diadenosine polyphosphates.
Institut National de la Santé et de la Recherche Médicale U. 390, Centre Hospitalier Universitaire Arnaud de Villeneuve, Montpellier, France. vassort@montp.inserm.fr
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D000227:Adenine Nucleotides / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001665:Binding Sites; D006321:Heart / Q000502:physiology*; D006801:Humans; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D014544:Uridine Triphosphate / Q000378:metabolism
D000227:Adenine Nucleotides; D018048:Receptors, Purinergic P2; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; D014544:Uridine Triphosphate