Ontogeny of the Adenylate Cyclase System in the Pulmonary Vascular Smooth Muscle of the Fetal Lamb

Abstract

The enzyme adenylate cyclase (AC) plays a critical role in regulation of vasodilatation in the developing pulmonary circulation. We characterized the ontogeny of the function of the AC system in the pulmonary vascular smooth muscle (VSM) of fetal lambs during the third trimester. Basal (nonstimulated) AC activity and activity with targeted stimulation of the components of the AC system were determined in pulmonary VSM plasma membranes from fetal lambs at 110-115 days (F-1) and 125-135 days of gestation (F-2) (with term being 144 +/- 3 days) and from pregnant ewes (adult) for comparison. We assessed beta-adrenergic receptor-mediated activity so that we could perform parallel studies of the VSM receptor binding characteristics. Basal AC activity declined 48% from F-1 to F-2 and an additional 13% from F-2 to adult. beta-Adrenergic receptor-stimulated activity was demonstrable only in adult pulmonary VSM membranes even though receptor density and affinity for the agonist were similar in fetal and adult pulmonary VSM. AC activity with NaF stimulation at the level of the G proteins declined 65% from F-1 to F-2 and was similar in F-2 as compared with adult. This indicates that the function of the G proteins or the catalytic subunit of the enzyme decreases from F-1 to F-2. The latter is suggested by the observation that AC activity with direct stimulation of the catalytic subunit with forskolin decreased 45% over this time period.(ABSTRACT TRUNCATED AT 250 WORDS)