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

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Abstract

The enzyme adenylate cyclase (AC) plays a critical role in regulation of vasodilation 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 β-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. β-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. 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 systemic 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 increase in responsiveness of the ovine fetal pulmonary circulation to vasoconstrictor influences during the third trimester.

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

Fingerprint

Vascular Smooth Muscle
Adenylyl Cyclases
Lung
Pulmonary Circulation
Third Pregnancy Trimester
Colforsin
GTP-Binding Proteins
Adrenergic Receptors
Membranes
Catalytic Domain
Fetal Movement
Vasoconstrictor Agents
Enzymes
Vasodilation
Sheep
Cell Membrane
Pregnancy

Keywords

  • β-Adrenergic receptor
  • [I]-Iodocyanopindolol
  • Forskolin
  • G protein
  • Guanosine triphosphate
  • Sodium fluoride

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pharmacology

Cite this

Ontogeny of the adenylate cyclase system in the pulmonary vascular smooth muscle of the fetal lamb. / Shaul, P. W.; Muntz, K. H.; DeBeltz, D.; Buja, L. M.

In: Journal of Cardiovascular Pharmacology, Vol. 17, No. 1, 1991, p. 125-133.

Research output: Contribution to journalArticle

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abstract = "The enzyme adenylate cyclase (AC) plays a critical role in regulation of vasodilation 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 β-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. β-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. 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 systemic 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 increase in responsiveness of the ovine fetal pulmonary circulation to vasoconstrictor influences during the third trimester.",
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