Dual control of DNA synthesis by alpha- and beta-adrenergic mechanisms in normoxic and hypoxic neonatal rat brain.
To examine how catecholamines influence cell replication in the developing brain, we examined regional [3H]thymidine incorporation into DNA after acute challenge with an alpha-adrenergic blocking agent (phenoxybenzamine) or a beta-blocker (propranolol). Phenoxybenzamine inhibited DNA synthesis in 1-day-old rat pups but the effect was less pronounced at 8 days; regional differences corresponded to transient expression of alpha-receptors and their subsequent maturational decline. Propranolol given at 1 day of age exerted a regionally selective, promotional effect on DNA synthesis; in contrast, at 8 days, propranolol inhibited DNA synthesis in all brain regions. Propranolol, but not phenoxybenzamine, also exacerbated the reduction in DNA synthesis caused by neonatal hypoxia, and again the effect was limited to the 1-day-old group. These results indicate that catecholamines exert a dual action on DNA synthesis; the effects are dependent upon maturational profiles of specific receptor populations which are either transiently expressed or which couple to cell replication only during a critical period.
Duncan
C P
CP
Department of Pharmacology, Duke University Medical Center, Durham, NC 27710.
Seidler
F J
FJ
Lappi
S E
SE
Slotkin
T A
TA
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism / Q000502:physiology*; D004261:DNA Replication / Q000187:drug effects*; D002534:Hypoxia, Brain / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D010643:Phenoxybenzamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D013936:Thymidine / Q000493:pharmacokinetics
D002395:Catecholamines; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D010643:Phenoxybenzamine; D010100:Oxygen; D013936:Thymidine