University Of Tasmania

File(s) under permanent embargo

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 contribution
posted on 2023-05-17, 10:05 authored by Cheung, NS, David SmallDavid Small, Livett, BG
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 25–35; 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 25–35. The IC50 of SP and βA4 25–35 was 3 × 10−6 and 3 × 10−5M, respectively. SP and βA4 25–35 both protected against nicotinic receptor desensitization. However, βA4 25–35 was ∼ 10-fold less effective than SP in its protective effect. The present work shows that βA4 25–35 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.


Publication title

Journal of Neurochemistry








Menzies Institute for Medical Research


Blackwell Publishing Ltd

Place of publication

9600 Garsington Rd, Oxford, England, Oxon, Ox4 2Dg

Rights statement

The definitive published version is available online at:

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified