Identification of β-Adrenergic Receptors Using [³H]Dihydroalprenolol in Fetal Sheep Heart: Direct Evidence of Qualitative Similarity to the Receptors in Adult Sheep Heart

Abstract

Summary: The fetal sheep heart responds to β-adrenergic stimuli; however, in vivo studies show the response of the fetal heart is less than that of the adult heart. We used [³H]dihydroalprenolol (DHA) to study directly β-adrenergic receptors in heart particulates of fetal sheep at term and adult sheep. [³H]DHA binding to fetal heart particulates was rapid, reversible (t_1/2 = 2.9 ± 0.3 min), stereoselective, saturable (101.2 ± 7.4 fmoles/mg protein), and of high affinity (4.8 ± 0.4 nM). The rank order of agonists competing for [³H]DHA binding was isoproterenol (0.32 ± 0.10 μM) > epinephrine (1.19 ± 0.23 μM) ⋍ norepinephrine (2.67 ± 0.69 μM), which is compatible with β₁-adrenergic potencies. [³H]DHA also bound to the adult sheep heart in a manner expected for β₁-receptors. No difference in the binding affinity of [³H]DHA or agonists' competition was demonstrated between the fetal and adult sheep heart. Comparison of the concentration of β-adrenergic receptors in fetal and adult hearts was confounded by the choice of the denominator for unit expression. The concentration was higher in the adult when expressed as a function of protein content or 5′-nucleotidase activity (0.52 ± 0.07 versus 1.12 ± 0.06). However, there was no difference when tissue weight, Na⁺ − K⁺-ATPase, or NaF-stimulated adenylate cyclase was used. Furthermore, isoproterenol-stimulated adenylate cyclase and cardiac contractile response to a threshold dose of isoproterenol were identical in the fetal and adult sheep heart. We conclude that β-receptors can be studied with [³H]DHA in the fetal sheep heart, this receptor is qualitatively similar to the β-receptor in the adult sheep heart, and it is unlikely that there is a difference in the concentration of β-adrenergic receptors in fetal and adult sheep heart.

Speculation: The interactions of adrenergic agents with cardiac β-adrenergic receptors in the term fetus are identical to those in the adult, and the receptor-adenylate cyclase coupling system reaches maturity before birth.

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