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.
Vassort
G
G
Institut National de la Santé et de la Recherche Médicale U. 390, Centre Hospitalier Universitaire Arnaud de Villeneuve, Montpellier, France. vassort@montp.inserm.fr
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