UTP but not ATP causes hypertrophic growth in neonatal rat cardiomyocytes.
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 microM) 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 microM) to cardiomyocytes caused hypertrophic growth indicated by increased protein content without DNA synthesis. ATP (100 microM) 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.
Pham
Tam M
TM
Cellular Biochemistry Laboratory, Baker Heart Research Institute, PO Box 6492, St. Kilda Road, Central, Vic. 8008, Melbourne, Australia.
Morris
James B
JB
Arthur
Jane F
JF
Post
Ginell R
GR
Brown
Joan Heller
JH
Woodcock
Elizabeth A
EA
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D006321:Heart / Q000254:growth & development*; D006984:Hypertrophy; D007527:Isoenzymes / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D054799:Phospholipase C beta; D051966:Phospholipase C gamma; D058915:Purinergic P1 Receptor Antagonists; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D010738:Type C Phospholipases / Q000378:metabolism; D014544:Uridine Triphosphate / Q000494:pharmacology*
D007527:Isoenzymes; D058915:Purinergic P1 Receptor Antagonists; D058919:Purinergic P2 Receptor Antagonists; D000255:Adenosine Triphosphate; D010738:Type C Phospholipases; D054799:Phospholipase C beta; D051966:Phospholipase C gamma; D014544:Uridine Triphosphate