UTP but not ATP causes hypertrophic growth in neonatal rat cardiomyocytes

• Published in: Journal of molecular and cellular cardiology 2003-03, Vol.35 (3), p.287-292
• Main Authors: Pham, Tam M., Morris, James B., Arthur, Jane F., Post, Ginell R., Brown, Joan Heller, Woodcock, Elizabeth A.
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - pharmacology; Animals; Animals, Newborn; Heart - growth & development; Hypertrophy; Isoenzymes - metabolism; Mitogen-activated protein kinase; Myocytes, Cardiac - cytology; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Neonatal cardiomyocyte; Phospholipase C beta; Phospholipase C gamma; PLC; Purinergic P1 Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic receptor; Rats; Rats, Sprague-Dawley; Type C Phospholipases - metabolism; Uridine Triphosphate - pharmacology
• ISSN: 0022-2828; 1095-8584
• DOI: 10.1016/S0022-2828(03)00009-9

Addition of ATP to neonatal rat cardiomyocytes has been reported to inhibit hypertrophic growth responses, even though G q-coupled receptors are activated. In the current study, we investigated hypertrophic responses to activation of G q-coupled-purinergic receptors on cardiomyocytes using UTP as an alternative agonist to ATP. UTP (100 μM) activated phospholipase C via G q similarly to ATP, and responses to the two agonists were not additive. Similarly, UTP and ATP both induced phosphorylation of extracellular signal-regulated kinase (ERK1/2), while having little effect on p38 mitogen-activated protein kinase or c-Jun NH 2-terminal kinase. However, addition of UTP (100 μM) to cardiomyocytes caused hypertrophic growth indicated by increased protein content without DNA synthesis. ATP (100 μM) caused no increase in protein. We conclude that activation of purinergic receptors on neonatal cardiomyocytes initiates hypertrophic signaling pathways, but that prolonged exposure to ATP, but not UTP, has growth-inhibitory effects.