Role of sympathetic neurons in development of beta-adrenergic control of ornithine decarboxylase activity in peripheral tissues: effects of neonatal 6-hydroxydopamine treatment.
Sympathetic neurons are thought to regulate the development of their postsynaptic targets. In the current study, we examined the effects of sympathectomy with 6-hydroxydopamine in neonatal rats on the ontogeny of beta-receptor binding sites and their linkage to both cyclic AMP production and ornithine decarboxylase activity. Cardiac norepinephrine levels and turnover were used to confirm the completeness and permanence of the lesion. The ability of isoproterenol, a beta-adrenergic agonist, to stimulate ornithine decarboxylase (a growth-related enzyme) in heart, lung and kidney, was reduced by neonatal sympathectomy; the effect persisted into young adulthood. The effect represented a selective uncoupling of enzyme activity from receptor activation, as receptor binding capabilities were unaffected and the linkage of beta-receptors to cyclic AMP was enhanced. Comparison of the effects of peripheral sympathectomy with those of central lesions (intracisternal 6-hydroxydopamine) confirmed the importance of sympathetic nerve terminals in determining the coupling of the receptors to ornithine decarboxylase. These data suggest that sympathetic neurons program their target organs to specific trophic responses during development.
Hou
Q C
QC
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710.
Baker
F E
FE
Seidler
F J
FJ
Bartolome
M
M
Bartolome
J
J
Slotkin
T A
TA
D000818:Animals; D000831:Animals, Newborn; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D006892:Hydroxydopamines; D007545:Isoproterenol / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology / Q000378:metabolism; D008168:Lung / Q000201:enzymology / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D009638:Norepinephrine / Q000032:analysis; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D016627:Oxidopamine; D011247:Pregnancy; D011897:Random Allocation; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013563:Sympathectomy, Chemical; D013564:Sympathetic Nervous System / Q000166:cytology / Q000502:physiology*
D006892:Hydroxydopamines; D011943:Receptors, Adrenergic, beta; D016627:Oxidopamine; D000242:Cyclic AMP; D009955:Ornithine Decarboxylase; D007545:Isoproterenol; D009638:Norepinephrine