A1 adenosine receptors potently regulate heart rate in mammalian embryos

Paul L. Hofman, Kelly Hiatt, Mervin C. Yoder, Scott A. Rivkees

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

A1 adenosine receptors (A1ARs) have been recently shown to be expressed in rodent embryonic hearts at very early stages of development. To determine the functional significance of fetal cardiac A1AR expression during embryogenesis, murine fetal heart preparations were studied between postconceptual days 9 and 12. Dose-response curves generated using a variety of adenosine agonists revealed that A1AR activation potently regulated fetal heart rates. The A1AR agonist, N6-cyclopentyladenosine, inhibited heart rates in a dose-dependent manner (half-maximal effective concentration = 3.6 x 10-8M) and stopped fetal cardiac contractions in 63% of preparations. In contrast, A2a and A2b receptor activation did not alter heart rates, and activation of A3 receptors produced modest declines in heart rates. Endogenous adenosine also acted tonically to suppress fetal heart rates, as demonstrated by the A1AR antagonist 1,3-dipropyl-8-cyclopentylxanthine, increasing heart rates, whereas the adenosine reuptake blocker dipyridamole lowered fetal heart rates. Pertussis toxin treatment blocked A1AR action, showing that A1AR action was G protein mediated. Using drugs that alter cAMP levels and ion channel action, we were able to show that A1AR action involves events mediated by cAMP, ATP-dependent K, L-type calcium, sodium, and chloride channels, and the pacemaker current. These data show that adenosine and A1ARs potently regulate mammalian heart rates via multiple effector systems at very early stages of prenatal development.

Original languageEnglish (US)
Pages (from-to)R1374-R1380
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume273
Issue number4 42-4
StatePublished - Nov 17 1997

Keywords

  • Adenosine
  • Fetus
  • Heart

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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