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Dual pathways regulate neurite outgrowth in enteric ganglia
D M Simeone1, G Romanchuk, M W Mulholland
1Department of Surgery, University of Michigan, Ann Arbor 48109-0331.
The American Journal of Physiology
|October 1, 1994
Summary
Agents that increase cyclic adenosine monophosphate (cAMP) levels promote the growth of enteric neurons. This growth is mediated by cAMP-dependent protein kinases, suggesting dual pathways regulate enteric ganglia development.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- The myenteric plexus is crucial for gastrointestinal function.
- Understanding enteric neuronal growth is vital for gut development and repair.
Purpose of the Study:
- To investigate the role of cyclic adenosine monophosphate (cAMP) in stimulating morphological growth of enteric neurons.
- To elucidate the signaling pathways involved in enteric neuronal development.
Main Methods:
- Primary cultures of guinea pig myenteric plexus ganglia were utilized.
- Agents activating adenylate cyclase or mimicking intracellular cAMP were applied.
- Neurite length and density were quantified.
- mRNA expression for alpha-tubulin and microtubule-associated protein 2 was analyzed.
Main Results:
- Forskolin, cholera toxin, and cAMP analogues significantly increased neurite length and density in a dose-dependent manner.
- A cAMP-dependent kinase inhibitor blocked the growth effects of cAMP analogues but not nerve growth factor (NGF).
- Activation of cAMP pathways upregulated mRNA for alpha-tubulin and microtubule-associated protein 2.
Conclusions:
- Elevated intracellular cAMP levels promote morphological growth in enteric neurons.
- Dual signaling pathways, involving NGF and cAMP-dependent protein kinases, regulate growth in enteric ganglia.
- cAMP-dependent signaling is a key mechanism in enteric neuronal development.