Ontogeny of the adenylate cyclase system in the pulmonary vascular smooth muscle of the fetal lamb

P. W. Shaul, K. H. Muntz, D. DeBeltz, L. M. Buja

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Ther enzyme adenylate cyclase (AC) plays a critical role in regulation of vasodilatation in the devel-oping pulmonary circulation. We characterizaed the ontogeney of the function of the AC system in the pulmonary vascular smooth muscle (VSM) of fetal ambs during the third trimester. Basal (non stimulated) AC activity and activioty 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 β-adrenergic recepto-mediated activityu so that we could perform parallel studies of the VSM receptor binding characteristcs. Basal Ac activity declined 48% from F-1 to F-2 and an additional 13% from F-2 to adult. β-Adrenergic receptor-stimulated activity was demonsirable only in adult pulmonary VSM membranes even though receptor density and affinity for the agonist were similar in setal 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. Because the maturational decline in basal AC activity in fetal VSM membranes parallels the decrease in NaF- and forskolin-stimulated activity, the observations for basal activity probably are related primarily to the Changes in postreceptor-mediated mechanisms. Concomitant studies of systemioc VSM membranes indicate that these developmental alterations are specific to the pulmonary VSM, This maturational decline in the function of the pulmonary VSM adenylate cyclase system may contribute to the inerease in responsivencess of the ovine fetal pulmonary circulation to vasoconstrictor influences during ther third trimester.

Original languageEnglish (US)
Pages (from-to)125-133
Number of pages9
JournalJournal of Cardiovascular Pharmacology
Volume17
Issue number1
DOIs
StatePublished - Jan 1991

Keywords

  • Forskolin
  • G Protein
  • Guanosine triphosphate
  • Sodium fluoride
  • [I]-lodocyanopindolol
  • β-Adrenergic receptor

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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