Exp Mol Med.  2006 Feb;38(1):85-93.

Secretin induces neurite outgrowth of PC12 through cAMP-mitogen-activated protein kinase pathway

• Kim HS
• Yumkham S
• Kim SH
• Yea K
• Shin YC
• Ryu SH
• Suh PG

Abstract

The gastrointestinal functions of secretin have been fairly well established. However, its function and mode of action within the nervous system remain largely unclear. To gain insight into this area, we have attempted to determine the effects of secretin on neuronal differentiation. Here, we report that secretin induces the generation of neurite outgrowth in pheochromocytoma PC12 cells. The expressions of Tau and beta-tubulin, neuronal differentiation markers, are increased upon secretin stimulation. In addition, secretin induces sustained mitogen-activated protein kinase (MAPK) activation and also stimulates the cAMP secretion. Moreover, the neurite outgrowth elicited by secretin is suppressed to a marked degree in the presence of either PD98059, a specific MAPK/ERK kinase (MEK) inhibitor, or H89, a specific protein kinase A (PKA) inhibitor. Taken together, these observations demonstrate that secretin induces neurite outgrowth of PC12 cells through cAMP-MAPK pathway, and provide a novel insight into the manner in which secretin participates in neuritogenesis.

Keyword

mitogen-activated protein kinases; neurites; pheochromocytoma; secretin; tau proteins

MeSH Terms

Animals
Cell Culture Techniques
Cell Differentiation/drug effects
Comparative Study
Cyclic AMP/analysis/metabolism
Enzyme-Linked Immunosorbent Assay
Fluorescein-5-isothiocyanate
Fluorescent Dyes
Immunoblotting
Immunohistochemistry
Microscopy, Confocal
Mitogen-Activated Protein Kinases/*metabolism
Neurites/*drug effects
Neurons/cytology/drug effects
PC12 Cells
Rats
Research Support, Non-U.S. Gov't
Reverse Transcriptase Polymerase Chain Reaction
Secretin/*pharmacology