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Imbalances emerge in cardiac autonomic cell signaling after neonatal exposure to terbutaline or chlorpyrifos, alone or in combination.

Publication ,  Journal Article
Slotkin, TA; Tate, CA; Cousins, MM; Seidler, FJ
Published in: Brain Res Dev Brain Res
December 7, 2005

During early neonatal development, the future reactivity of the heart to cardiac autonomic stimulation is programmed by the timing and intensity of the arrival of parasympathetic and sympathetic inputs. In neonatal rats, we examined the effects of exposure to terbutaline, a beta-adrenoceptor (betaAR) agonist used to arrest preterm labor, and chlorpyrifos (CPF), a widely used organophosphate pesticide that acts in part through inhibition of cholinesterase, using scenarios mimicking the likely developmental stages corresponding to peak human exposures: postnatal days (PN) 2-5 for terbutaline and PN11-14 for CPF. Terbutaline evoked a progressive deficit in cardiac betaAR binding but did not interfere with the ability of the receptors to stimulate adenylyl cyclase (AC). Terbutaline also reduced expression of m2 muscarinic acetylcholine receptors and suppressed their ability to inhibit AC. Surprisingly, CPF produced similar actions, a decrement in betaAR and m2 muscarinic receptor binding and a loss of the cholinergic AC response, and also augmented the ability of betaARs to stimulate AC. The effects of CPF are thus unlikely to reside in cholinergic hyperstimulation resulting from cholinesterase inhibition but instead involve other actions converging on receptors and cell signaling. Exposure to both agents, terbutaline followed by CPF, produced a summation of the two individual effects. Our findings at the level of cell signaling thus indicate that neonatal exposure to terbutaline or CPF, or sequentially to both agents, results in an imbalance of cardiac autonomic inputs favoring increased excitability, an outcome that may have an impact on cardiovascular responses.

Duke Scholars

Published In

Brain Res Dev Brain Res

DOI

ISSN

0165-3806

Publication Date

December 7, 2005

Volume

160

Issue

2

Start / End Page

219 / 230

Location

Netherlands

Related Subject Headings

  • Terbutaline
  • Signal Transduction
  • Sex Factors
  • Receptors, Adrenergic, beta
  • Receptor, Muscarinic M2
  • Rats, Sprague-Dawley
  • Rats
  • Random Allocation
  • Protein Binding
  • Pregnancy
 

Citation

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Chicago
ICMJE
MLA
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Slotkin, T. A., Tate, C. A., Cousins, M. M., & Seidler, F. J. (2005). Imbalances emerge in cardiac autonomic cell signaling after neonatal exposure to terbutaline or chlorpyrifos, alone or in combination. Brain Res Dev Brain Res, 160(2), 219–230. https://doi.org/10.1016/j.devbrainres.2005.09.006
Slotkin, Theodore A., Charlotte A. Tate, Mandy M. Cousins, and Frederic J. Seidler. “Imbalances emerge in cardiac autonomic cell signaling after neonatal exposure to terbutaline or chlorpyrifos, alone or in combination.Brain Res Dev Brain Res 160, no. 2 (December 7, 2005): 219–30. https://doi.org/10.1016/j.devbrainres.2005.09.006.
Slotkin TA, Tate CA, Cousins MM, Seidler FJ. Imbalances emerge in cardiac autonomic cell signaling after neonatal exposure to terbutaline or chlorpyrifos, alone or in combination. Brain Res Dev Brain Res. 2005 Dec 7;160(2):219–30.
Slotkin, Theodore A., et al. “Imbalances emerge in cardiac autonomic cell signaling after neonatal exposure to terbutaline or chlorpyrifos, alone or in combination.Brain Res Dev Brain Res, vol. 160, no. 2, Dec. 2005, pp. 219–30. Pubmed, doi:10.1016/j.devbrainres.2005.09.006.
Slotkin TA, Tate CA, Cousins MM, Seidler FJ. Imbalances emerge in cardiac autonomic cell signaling after neonatal exposure to terbutaline or chlorpyrifos, alone or in combination. Brain Res Dev Brain Res. 2005 Dec 7;160(2):219–230.
Journal cover image

Published In

Brain Res Dev Brain Res

DOI

ISSN

0165-3806

Publication Date

December 7, 2005

Volume

160

Issue

2

Start / End Page

219 / 230

Location

Netherlands

Related Subject Headings

  • Terbutaline
  • Signal Transduction
  • Sex Factors
  • Receptors, Adrenergic, beta
  • Receptor, Muscarinic M2
  • Rats, Sprague-Dawley
  • Rats
  • Random Allocation
  • Protein Binding
  • Pregnancy