Ontogeny of beta-adrenergic regulation of adenylate cyclase in intrapulmonary arteries from fetal and postnatal lambs.
The enzyme adenylate cyclase is critically involved in the regulation of vasodilatation in the developing pulmonary circulation in that it mediates the vascular smooth muscle effects of beta-adrenergic agonists and vasodilatory prostaglandins. These agonists activate receptors coupled to the catalytic subunit of the enzyme by stimulatory guanine nucleotide-dependent regulatory proteins. We examined the ontogeny of the function of the adenylate cyclase system in intrapulmonary arterial segments from fetal lambs at 110-115 (F1) and 125-135 d gestation (F2) and from postnatal lambs at 7-14 (P1) and 35-56 d of age (P2). The function of the intact enzyme system and its components was assessed in incubations measuring cAMP accumulation during phosphodiesterase inhibition. beta-Adrenergic mediation of adenylate cyclase was examined because the binding characteristics of the smooth muscle receptors can be readily quantified. Nonstimulated (basal) cAMP accumulation was similar in F1 and F2, it increased 8-fold from F2 to P1, and it was equivalent in P1 and P2. cAMP accumulation with isoproterenol increased 5.9-fold from F1 to F2 and was similar in F2, P1, and P2. Radioligand binding studies revealed that the greater response to isoproterenol in F2 versus F1 is not related to an increase in beta-adrenergic receptor density or affinity. cAMP accumulation with forskolin, which activates adenylate cyclase by actions that involve both the stimulatory guanine nucleotide-dependent regulatory protein and the catalytic subunit, was similar in the four age groups, indicating that there are no maturational changes in the funciton of these enzyme system components.(ABSTRACT TRUNCATED AT 250 WORDS)
Shaul
P W
PW
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235.
Farrar
M A
MA
Buja
L M
LM
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011651:Pulmonary Artery / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D012756:Sheep; D014664:Vasodilation / Q000187:drug effects
D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol