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Role of presynaptic input in the ontogeny of adrenergic cell signaling in rat brain: beta receptors, adenylate cyclase and c-fos protooncogene expression.

Publication ,  Journal Article
Wagner, JP; Seidler, FJ; Lappi, SE; McCook, EC; Slotkin, TA
Published in: J Pharmacol Exp Ther
April 1995

Neurotransmitters act as trophic factors during brain development, regulating expression of genes that control cellular differentiation. One example of this trophism is the beta adrenergic signaling cascade: activation of beta receptors leads sequentially to increased cyclic AMP (cAMP), augmented expression of the nuclear transcription factor, c-fos, and induction of ornithine decarboxylase (ODC), an enzyme obligatory for neuronal development. After neonatal lesioning of noradrenergic nerves with 6-hydroxydopamine (6-OHDA), beta receptors become uncoupled from ODC induction in the cerebellum, a region that undergoes its peak of cell replication/differentiation postnatally. The present study investigates the mechanism for uncoupling of beta receptors from response elements. In the cerebellum, 6-OHDA had minor effects on beta receptor binding capabilities and caused slight supersensitivity of the beta adrenergic response of adenylate cyclase; the latter reflected increased expression of cyclase catalytic subunits, rather than a specific effect on beta receptor coupling. In contrast, the linkage of cAMP to cerebellar c-fos expression showed marked deficiencies in lesioned animals and a corresponding loss of the ability of beta receptors to induce c-fos; accordingly, this is a likely point at which beta adrenergic control of ODC is programmed by neuronal input. A critical period exists for neurotrophic influence: the alterations persisted past the point at which cerebellar norepinephrine levels recovered, and comparable effects did not occur in earlier-developing regions. In the forebrain, for example, neonatal lesions produced receptor upregulation and supersensitivity of c-fos to cAMP stimulation. These results suggest that presynaptic input is vital in programming beta adrenergic responsiveness during a critical period of development, and that interruption of transsynaptic events occurring at this time can lead to lasting alterations in neuronal differentiation and responsiveness.

Duke Scholars

Published In

J Pharmacol Exp Ther

ISSN

0022-3565

Publication Date

April 1995

Volume

273

Issue

1

Start / End Page

415 / 426

Location

United States

Related Subject Headings

  • Receptors, Adrenergic, beta
  • Rats, Sprague-Dawley
  • Rats
  • Pregnancy
  • Pharmacology & Pharmacy
  • Oxidopamine
  • Ornithine Decarboxylase
  • Isoproterenol
  • Genes, fos
  • GTP-Binding Proteins
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Wagner, J. P., Seidler, F. J., Lappi, S. E., McCook, E. C., & Slotkin, T. A. (1995). Role of presynaptic input in the ontogeny of adrenergic cell signaling in rat brain: beta receptors, adenylate cyclase and c-fos protooncogene expression. J Pharmacol Exp Ther, 273(1), 415–426.
Wagner, J. P., F. J. Seidler, S. E. Lappi, E. C. McCook, and T. A. Slotkin. “Role of presynaptic input in the ontogeny of adrenergic cell signaling in rat brain: beta receptors, adenylate cyclase and c-fos protooncogene expression.J Pharmacol Exp Ther 273, no. 1 (April 1995): 415–26.
Wagner JP, Seidler FJ, Lappi SE, McCook EC, Slotkin TA. Role of presynaptic input in the ontogeny of adrenergic cell signaling in rat brain: beta receptors, adenylate cyclase and c-fos protooncogene expression. J Pharmacol Exp Ther. 1995 Apr;273(1):415–26.
Wagner JP, Seidler FJ, Lappi SE, McCook EC, Slotkin TA. Role of presynaptic input in the ontogeny of adrenergic cell signaling in rat brain: beta receptors, adenylate cyclase and c-fos protooncogene expression. J Pharmacol Exp Ther. 1995 Apr;273(1):415–426.

Published In

J Pharmacol Exp Ther

ISSN

0022-3565

Publication Date

April 1995

Volume

273

Issue

1

Start / End Page

415 / 426

Location

United States

Related Subject Headings

  • Receptors, Adrenergic, beta
  • Rats, Sprague-Dawley
  • Rats
  • Pregnancy
  • Pharmacology & Pharmacy
  • Oxidopamine
  • Ornithine Decarboxylase
  • Isoproterenol
  • Genes, fos
  • GTP-Binding Proteins