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.
The amyloid protein (beta A4) 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 beta A4 (beta A4 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(-5) M nicotine was inhibited by SP and beta A4 25-35. The IC50 of SP and beta A4 25-35 was 3 x 10(-6) and 3 x 10(-5) M, respectively. SP and beta A4 25-35 both protected against nicotine receptor desensitization. However, beta A4 25-35 was approximately 10-fold less effective than SP in its protective effect. The present work shows that beta A4 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.
Cheung
N S
NS
Department of Biochemistry, University of Melbourne, Parkville, Victoria, Australia.
Small
D H
DH
Livett
B G
BG
D000311:Adrenal Glands / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000502:physiology*; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D002838:Chromaffin System / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D009538:Nicotine / Q000494:pharmacology*; D009994:Osmolar Concentration; D010446:Peptide Fragments / Q000494:pharmacology*; D013373:Substance P / Q000502:physiology*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D013373:Substance P; D009538:Nicotine