Inhibition of cell proliferation in the embryonic myocardium by A1 adenosine receptor activation.
A1 adenosine receptors (A1ARs) are expressed in the embryonic heart and influence cardiac function at early developmental stages. To test if A1ARs also affect cardiac structural development, we examined the effects of A1AR activation on heart formation. When pregnant mice were treated with the A1AR agonist, N(6)-cyclopentyladenosine (CPA), fetuses showed marked reduction of ventricular size and manifested features of heart failure. Suggesting that these findings represent direct effects on embryos, CPA treatment of cultured whole murine embryos resulted in cardiac hypoplasia. When rates of cell division and cell death in the heart were examined, we found decreases in cardiac cell proliferation following A1AR activation. In contrast, no changes in numbers or distribution of apoptotic cells were seen. Collectively, these data show that A1AR activation inhibits cardiac cell proliferation and can lead to cardiac hypoplasia. These data identify adenosine as a potential regulator of cardiac cell division during early development.
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Yale Child Health Research Center, Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06520, USA.
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D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D017209:Apoptosis; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006321:Heart / Q000196:embryology*; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D009206:Myocardium / Q000166:cytology*; D009924:Organ Culture Techniques; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D013997:Time Factors
D018047:Receptors, Purinergic P1; C048599:N(6)-cyclopentyladenosine; D001973:Bromodeoxyuridine; D000241:Adenosine