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An Amyloid Peptide, βA 4 25–35, Mimics the Function of Substance P on Modulation of Nicotine‐Evoked Secretion and Desensitization in Cultured Bovine Adrenal Chromaffin Cells
Author(s) -
Cheung Nam Sang,
Small David H.,
Livett Bruce G.
Publication year - 1993
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1993.tb03270.x
Subject(s) - nicotinic agonist , nicotine , endocrinology , medicine , substance p , desensitization (medicine) , secretion , peptide , endogeny , receptor , neuropeptide , amyloid (mycology) , chromaffin cell , chemistry , nicotinic antagonist , acetylcholine , biology , biochemistry , adrenal medulla , catecholamine , inorganic chemistry
The amyloid protein (βA 4 ) 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 βA 4 βA 4 25–35; Gly‐Ser‐Asn‐Lys‐Gly‐Ala‐Ile‐Ile‐Gly‐Leu‐Met‐NH 2 ), which contains the conserved C‐terminal sequence of substance P (X‐Gly‐Leu‐Met‐NH 2 ), 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 −5 M nicotine was inhibited by SP and βA 4 25–35. The IC 50 of SP and βA 4 25–35 was 3 × 10 −6 and 3 × 10 −5 M , respectively. SP and βA 4 25–35 both protected against nicotinic receptor desensitization. However, βA 4 25–35 was ∼ 10‐fold less effective than SP in its protective effect. The present work shows that βA 4 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.