378 ONTOGENY OF β-ADRENERGIC RECEPTORS IN MAMMALIAN LUNG

Abstract

The ontogeny of β-adrenergic receptors (BAR) in lung was described in the rabbit, rat, sheep and guinea pig. Developmental increases in binding capacity were demonstrated in all species, for example, rabbit lung membrane bound (-)-[³H]-dihydroalprenolol, [³H]DHA to a single class of sites, was stereoselective, reversible and saturable; K_D 1.78±0.30 nM. Binding at all ages was inhibited by agonists in the order of potency: Iso > Epi=Norepi characteristic of a β₁AR subtype. Studies with metoprolol (β₁) and zinterol (β₂-selective) revealed 60% β₁- and 40% β₂adrenergic subtypes at all ages. Bmax increased 11.5 fold from day 25 of gestation to adulthood, increasing during the latter days of gestation and the early neonatal period, from 37±10 fmolemg^-1 protein to 425±51 in the adult, m±SD. Gpp(NH)p decreased agonist affinity more effectively in adult than in fetal lung and we hypothesize that a “coupling” defect exists in fetal lung BAR. The sensitivity of adenylate cyclase activity to catecholamine was maximal in adult rabbit lung increasing with age from 23% at day 25 gestation to 255% stimulation in the adult. Pulmonary BAR numbers at term gestation were higher in animals which are relatively more mature at birth (guinea pig and sheep) as compared to less mature (rabbit and rat). In conclusion, β-adrenergic receptors appear to be a sensitive indicator of pulmonary maturation and the increase in BAR during development in mammalian lung and supports the role of β-adrenergic receptors in the regulation of pulmonary function.

Log in or create a free account to read this content

Gain free access to this article, as well as selected content from this journal and more on nature.com

Access through your institution

or

Sign in or create an account

Continue with Google

Continue with ORCiD