Ontogeny of mammalian myocardial β-adrenergic receptors

Little information is available regarding the ontogenesis of the mammalian cardiac β-receptor and its relationship to physiological responses. In this study, β-adrenergic receptors were identified and characterized in the fetal, neonatal, and adult mouse heart using [³H]-(-)-dihydroalprenolol ([³H]-DHA). The fetal mouse heart (FMH) in organ culture was used to study the development of responsiveness to the β-agonist, (-)-isoproterenol. Whereas 13 day (d) fetal mouse hearts were insensitive to (-)-isoproterenol, hearts from 21 d fetal mouse responded to (-)-isoproterenol with an approximate doubling of the heart rate. The dissociation constant (K_D) of [³H]-DHA for the β-adrenergic receptor (0.3 nM) remained unaltered during development. In contrast, β-adrenergic receptor density expressed as percentage of the adult receptor density was: 14% for 13 d FMH; 29% for 15 d FMH; 41% for 17 d FMH; 65% for 19 d FMH; 73% for 21 d FMH; 93% for 1 d neonate; 168% for 3 d neonate, and 173% for 14 d neonate. These data suggest that the β-adrenergic receptor, detected by [³H]-DHA binding, (1) appears prior to a detectable heart rate response, (2) has significant increases during the third trimester which parallel the increased adrenergic responsiveness, and (3) dramatically increases in the postnatal period before declining to the adult level.