In:
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, American Physiological Society, Vol. 273, No. 4 ( 1997-10-01), p. R1374-R1380
Abstract:
A 1 adenosine receptors (A 1 ARs) 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 A 1 AR 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 A 1 AR activation potently regulated fetal heart rates. The A 1 AR agonist, N 6 -cyclopentyladenosine, inhibited heart rates in a dose-dependent manner (half-maximal effective concentration = 3.6 × 10 −8 M) and stopped fetal cardiac contractions in 63% of preparations. In contrast, A 2 a and A 2 b receptor activation did not alter heart rates, and activation of A 3 receptors produced modest declines in heart rates. Endogenous adenosine also acted tonically to suppress fetal heart rates, as demonstrated by the A 1 AR antagonist 1,3-dipropyl-8-cyclopentylxanthine, increasing heart rates, whereas the adenosine reuptake blocker dipyridamole lowered fetal heart rates. Pertussis toxin treatment blocked A 1 AR action, showing that A 1 AR action was G protein mediated. Using drugs that alter cAMP levels and ion channel action, we were able to show that A 1 AR 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 A 1 ARs potently regulate mammalian heart rates via multiple effector systems at very early stages of prenatal development.
Type of Medium:
Online Resource
ISSN:
0363-6119
,
1522-1490
DOI:
10.1152/ajpregu.1997.273.4.R1374
Language:
English
Publisher:
American Physiological Society
Publication Date:
1997
detail.hit.zdb_id:
1477297-8
SSG:
12
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