Adenylate cyclase and beta adrenergic receptor development in the mouse heart

We have demonstrated previously a postnatal peak for the beta adrenergic receptor in the heart and detected the appearance of a beta adrenergic receptor before an (-)-isoproterenol inducible increase in heart rate. The present study examined (1) agonist displaceable [³H]dihydroalprenolol (DHA) binding in the neonatal and adult mouse heart and (2) adenylate cyclase in fetal, neonatal and adult mouse heart. [³H]DHA binding displaceable by (-)-isoproterenol gave a similar K₁ from 1 day neonate through adult. Similar to the result found for antagonist displacement binding, there was a dramatic increase in the agonist displacement [³H]DHA binding postnatally. The maximum was achieved in 2 weeks and then gradually declined to adult level. Cyclase activity (basal, (-)-isoproterenol- and NaF-stimulated) paralleled beta adrenergic receptor increases before birth. However, no early postnatal peak was present. In the 13 day fetal mouse heart, there is no (-)-isoproterenol increase in heart rate, but beta adrenergic receptor (13 ± 4% of adult) and (-)-isoproterenol-stimulated adenylate cyclase activity (15 ± 5% of adult) are present. It is concluded that (1) no significant difference exists between the agonist and antagonist displaceable [³H]DHA binding during development, (2) adenylate cyclase activity increases significantly during the last third of pregnancy in parallel with the beta adrenergic receptor, (3) both the beta adrenergic receptor and adenylate cyclase activity can be detected before the heart rate responses and (4) total adenylate cyclase activity does not increase in parallel with the early postnatal beta adrenergic receptor peak.