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Effects of Ciliary Neurotrophic Factor (CNTF) and Depolarization on Neuropeptide Expression in Cultured Sympathetic Neurons

Rao, M. S. and Tyrrell, S. and Landis, S. C. and Patterson, P. H. (1992) Effects of Ciliary Neurotrophic Factor (CNTF) and Depolarization on Neuropeptide Expression in Cultured Sympathetic Neurons. Developmental Biology, 150 (2). pp. 281-293. ISSN 0012-1606. doi:10.1016/0012-1606(92)90242-9. https://resolver.caltech.edu/CaltechAUTHORS:20160308-075957648

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Abstract

We examined the effects of ciliary neurotrophic factor (CNTF) and depolarization, two environmental signals that influence noradrenergic and cholinergic function, on neuropeptide expression by cultured sympathetic neurons. Sciatic nerve extract, a rich source of CNTF, increased levels of vasoactive intestinal peptide (VIP), substance P, and somatostatin severalfold while significantly reducing levels of neuropeptide Y (NPY). No change was observed in the levels of leu-enkephalin (L-Enk). These effects were abolished by immunoprecipitation of CNTF-like molecules from the extract with an antiserum raised against recombinant CNTF, and recombinant CNTF caused changes in neuropeptide levels similar to those of sciatic nerve extract. Alterations in neuropeptide levels by CNTF were dose-dependent, with maximal induction at concentrations of 5–25 ng/ml. Peptide levels were altered after only 3 days of CNTF exposure and continued to change for 14 days. Depolarization of sympathetic neuron cultures with elevated potassium elicited a different spectrum of effects; it increased VIP and NPY content but did not alter substance P, somatostatin, or L-Enk. Depolarization is known to block cholinergic induction in response to heart cell conditioned medium and we found that it blocked the induction of choline acetyltransferase (ChAT) and peptides by recombinant cholinergic differentiation factor/leukemia inhibitory factor (CDF/LIF). In contrast, it did not antagonize the effects of CNTF on either ChAT activity or neuropeptide expression. Thus, while CNTF has effects on neurotransmitter properties similar to those previously reported for CDF/LIF, the actions of these two factors are differentially modulated by depolarization, suggesting that the mechanisms of cholinergic and neuropeptide induction for the two factors differ. In addition, in contrast to CDF/LIF, CNTF did not alter levels of ChAT, VIP, substance P, or somatostatin in cultured dorsal root ganglion neurons. These observations indicate that CNTF and depolarization affect the expression of neuropeptides by sympathetic neurons and provide evidence for an overlapping yet distinct spectrum of actions of the two neuronal differentiation factors, CNTF and CDF/LIF.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/0012-1606(92)90242-9DOIArticle
http://www.sciencedirect.com/science/article/pii/0012160692902429PublisherArticle
Additional Information:© 1992 Academic Press, Inc. Accepted 2 December 1991. The authors thank Dr. Ken Neet for providing NGF and Regeneron Pharmaceuticals for recombinant CNTF and the anti-CNTF antiserum. This work was supported by an NINDS Javits Neuroscience Investigator Award and a McKnight Foundation Neuroscience Research Project Award to P.H.P. and by HD 25681 to S.C.L. Dr. Rao is the recipient of a postdoctoral fellowship from the Northeast Ohio Affiliate of the American Heart Association. S. Tyrrell was supported by GM 07250.
Funders:
Funding AgencyGrant Number
National Institute of Neurological Disorders and Stroke (NINDS)UNSPECIFIED
McKnight FoundationUNSPECIFIED
NIHHD 25681
American Heart Association, Northeast Ohio AffiliateUNSPECIFIED
NIHGM 07250
Issue or Number:2
DOI:10.1016/0012-1606(92)90242-9
Record Number:CaltechAUTHORS:20160308-075957648
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20160308-075957648
Official Citation:M.S. Rao, S. Tyrrell, S.C. Landis, P.H. Patterson, Effects of ciliary neurotrophic factor (CNTF) and depolarization on neuropeptide expression in cultured sympathetic neurons, Developmental Biology, Volume 150, Issue 2, April 1992, Pages 281-293, ISSN 0012-1606, http://dx.doi.org/10.1016/0012-1606(92)90242-9. (http://www.sciencedirect.com/science/article/pii/0012160692902429)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:65175
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:09 Mar 2016 20:58
Last Modified:10 Nov 2021 23:41

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