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C-type natriuretic peptide is a Schwann cell-derived factor for development and function of sensory neurons


Cyclic GMP (cGMP) is known to play important roles for neuronal development and neurite pathfinding. However, the regulatory mechanism which governs the synthesis of cGMP in the nervous system is not well defined. In the present study, we examined the role of C-type natriuretic peptide (CNP), which increases intracellular cGMP upon binding to its receptor, guanylyl cyclase (GC)-B, in the peripheral nervous system.

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Immunohistochemistry revealed that CNP is demonstrated in Schwann cells, whereas GC-B mRNA is highly expressed in dorsal root ganglion (DRG) neurons. In cultured DRG neurons, GC-B was demonstrated in dendrites of TrkA-positive cells, where it co-exists with cGMP-dependent protein kinase I (cGKI), the major intracellular mediator of cGMP actions. Addition of CNP in the culture medium apparently increased the density of fine neurites, which was accompanied by the increase in phosphorylation of vasodilator-stimulated phosphoprotein (VASP), a cGKI substrate. Furthermore, in the mice deficient for CNP gene (CNP-KO), the numbers of TrkA-positive DRG neurons were diminished. Likewise, there were much less cGKI-positive neurons in DRG and cGKI-positive fibers in dorsal spinal cord of CNP-KO than wild type mice. Finally, CNP-KO mice displayed a decreased response to inflammatory pain compared to wild types.


Taken together, these results suggest that CNP is derived from Schwann cells and plays an important role for the development and function of nociceptve sensory neurons.

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Correspondence to Ichiro Kishimoto.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Kishimoto, I., Tokudome, T., Chusho, H. et al. C-type natriuretic peptide is a Schwann cell-derived factor for development and function of sensory neurons. BMC Pharmacol 9 (Suppl 1), P33 (2009).

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