DRUGS AND DEVELOPMENT OF THE ADRENERGIC NERVOUS SYSTEM

Summary

Principal Investigator: Theodore Slotkin
Affiliation: Duke University Medical Center
Country: USA
Abstract: DESCRIPTION: (Adapted from the Investigator's Abstract): The current renewal will determine the cellular mechanisms underlying agonist-induced sensitization and the biochemical, structural, and physiological consequences of pharmacologic overstimulation of cardiac fetal beta-receptors by terbutaline. They will then go on to evaluate what cellular and molecular events occur within the postnatal period to replace fetal agonist-induced sensitization with the mature mechanism, agonist-induced desensitization. The aims are: 1. To determine what cellular mechanisms govern the ontogeny of agonist-induced beta-receptor downregulation and uncoupling from response elements in the developing heart; 2. To determine the mechanisms underlying fetal agonist induced sensitization of cardiac adenylyl cyclase; to determine the structural and functional consequences of fetal overstimulation with terbutaline during the period in which desensitization cannot be evoked.
Funding Period: 1976-06-15 - 2005-05-31
more information: NIH RePORT

Top Publications

  1. ncbi Developmental exposure to terbutaline and chlorpyrifos: pharmacotherapy of preterm labor and an environmental neurotoxicant converge on serotonergic systems in neonatal rat brain regions
    Justin E Aldridge
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA
    Toxicol Appl Pharmacol 203:132-44. 2005
  2. ncbi Developmental exposure to terbutaline alters cell signaling in mature rat brain regions and augments the effects of subsequent neonatal exposure to the organophosphorus insecticide chlorpyrifos
    Armando Meyer
    Centro de Estudos da Saúde do Trabalhador e Ecologia Humana AM, Escola Nacional de Saude Publica, Fundacao Oswaldo Cruz, Rio de Janeiro, Brazil
    Toxicol Appl Pharmacol 203:154-66. 2005
  3. ncbi Gestational dexamethasone treatment elicits sex-dependent alterations in locomotor activity, reward-based memory and hippocampal cholinergic function in adolescent and adult rats
    Marisa L Kreider
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA
    Neuropsychopharmacology 30:1617-23. 2005
  4. ncbi Disruption of rat forebrain development by glucocorticoids: critical perinatal periods for effects on neural cell acquisition and on cell signaling cascades mediating noradrenergic and cholinergic neurotransmitter/neurotrophic responses
    Marisa L Kreider
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Research Drive, Durham, NC 27710, USA
    Neuropsychopharmacology 30:1841-55. 2005
  5. ncbi Lasting effects of developmental dexamethasone treatment on neural cell number and size, synaptic activity, and cell signaling: critical periods of vulnerability, dose-effect relationships, regional targets, and sex selectivity
    Marisa L Kreider
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, USA
    Neuropsychopharmacology 31:12-35. 2006
  6. ncbi Critical periods for the role of oxidative stress in the developmental neurotoxicity of chlorpyrifos and terbutaline, alone or in combination
    Theodore A Slotkin
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA
    Brain Res Dev Brain Res 157:172-80. 2005

Scientific Experts

  • Theodore A Slotkin
  • Marisa L Kreider
  • Frederic J Seidler
  • Justin E Aldridge
  • Armando Meyer
  • Colleen A Oliver
  • Mandy M Cousins
  • Charlotte A Tate
  • Edward D Levin

Detail Information

Publications6

  1. ncbi Developmental exposure to terbutaline and chlorpyrifos: pharmacotherapy of preterm labor and an environmental neurotoxicant converge on serotonergic systems in neonatal rat brain regions
    Justin E Aldridge
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA
    Toxicol Appl Pharmacol 203:132-44. 2005
    ..Our results indicate that 5HT systems represent a target for otherwise unrelated neuroteratogens...
  2. ncbi Developmental exposure to terbutaline alters cell signaling in mature rat brain regions and augments the effects of subsequent neonatal exposure to the organophosphorus insecticide chlorpyrifos
    Armando Meyer
    Centro de Estudos da Saúde do Trabalhador e Ecologia Humana AM, Escola Nacional de Saude Publica, Fundacao Oswaldo Cruz, Rio de Janeiro, Brazil
    Toxicol Appl Pharmacol 203:154-66. 2005
    ....
  3. ncbi Gestational dexamethasone treatment elicits sex-dependent alterations in locomotor activity, reward-based memory and hippocampal cholinergic function in adolescent and adult rats
    Marisa L Kreider
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA
    Neuropsychopharmacology 30:1617-23. 2005
    ....
  4. ncbi Disruption of rat forebrain development by glucocorticoids: critical perinatal periods for effects on neural cell acquisition and on cell signaling cascades mediating noradrenergic and cholinergic neurotransmitter/neurotrophic responses
    Marisa L Kreider
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Research Drive, Durham, NC 27710, USA
    Neuropsychopharmacology 30:1841-55. 2005
    ..These results indicate that, during a critical developmental period, Dex administration leads to widespread interference with forebrain development, likely contributing to eventual, adverse neurobehavioral outcomes...
  5. ncbi Lasting effects of developmental dexamethasone treatment on neural cell number and size, synaptic activity, and cell signaling: critical periods of vulnerability, dose-effect relationships, regional targets, and sex selectivity
    Marisa L Kreider
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, USA
    Neuropsychopharmacology 31:12-35. 2006
    ..These results indicate that, during critical developmental periods, Dex administration evokes lasting alterations in neural cell numbers and synaptic function in forebrain regions, even at doses below those used in preterm infants...
  6. ncbi Critical periods for the role of oxidative stress in the developmental neurotoxicity of chlorpyrifos and terbutaline, alone or in combination
    Theodore A Slotkin
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA
    Brain Res Dev Brain Res 157:172-80. 2005
    ....