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An amyloid peptide beta-A4 25-35, mimics the function of substance P on modulation of nicotine-evoked secretion and desensitization in cultured bovine adrenal chromaffin cells

Citation

Cheung, NS and Small, DH and Livett, BG, An amyloid peptide beta-A4 25-35, mimics the function of substance P on modulation of nicotine-evoked secretion and desensitization in cultured bovine adrenal chromaffin cells, Journal of Neurochemistry, 60, (3) pp. 1163-1166. ISSN 0022-3042 (1993) [Refereed Article]


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The definitive published version is available online at: http://www3.interscience.wiley.com/

DOI: doi:10.1111/j.1471-4159.1993.tb03270.x

Abstract

The amyloid protein (βA4) is found in the CNS of patients with Alzheimer's disease; however, the pathogenic role of this protein is not known. In the present study, a peptide fragment of βA4βA4 2535; Gly-Ser-Asn-Lys-Gly-Ala-Ile-Ile-Gly-Leu-Met-NH2), which contains the conserved C-terminal sequence of substance P (X-Gly-Leu-Met-NH2), and the neuropeptide substance P (SP) were examined for their ability to modulate nicotine-evoked secretion from cultured bovine adrenal chromaffin cells. Secretion of the released endogenous catecholamines was monitored by electrochemical detection after separation by HPLC. Secretion induced by 10−5M nicotine was inhibited by SP and βA4 2535. The IC50 of SP and βA4 2535 was 3 10−6 and 3 10−5M, respectively. SP and βA4 2535 both protected against nicotinic receptor desensitization. However, βA4 2535 was ∼ 10-fold less effective than SP in its protective effect. The present work shows that βA4 2535 can mimic the modulatory actions of SP on the nicotinic response of cultured bovine chromaffin cells, i.e., inhibition of the nicotinic response and protection against nicotinic desensitization. These modulatory actions may be associated with changes in nicotinic receptor levels reported to occur in Alzheimer's disease.

Item Details

Item Type:Refereed Article
Keywords: Substance P; Tachykinin; Peptide analogue; β-Amyloid protein; Alzheimer's disease; Bovine adrenal chromaffin cells
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Neurosciences not elsewhere classified
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Neurodegenerative Disorders Related to Ageing
Author:Small, DH (Professor David Small)
ID Code:75432
Year Published:1993
Web of Science® Times Cited:34
Deposited By:Research Division
Deposited On:2012-01-30
Last Modified:2012-02-01
Downloads:0

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