title: Effects of soluble β-amyloid on the release of neurotransmitters from rat brain synaptosomes.
abstract: Contradictory results have been reported on the interaction of beta-amyloid (Aβ) with cholinergic receptors. The present paper investigates the modulatory effect of Aβ1-40 on the neurotransmitter release evoked by nicotinic (nAChRs) and muscarinic (mAChRs) receptors. Aβ1-40 inhibits both nicotinic and muscarinic-evoked [(3)H]DA overflow from rat nerve endings. Added to perfusion medium, Aβ1-40 is able to enter into synaptosomes; it exerts its inhibitory effect at extracellular sites when release is stimulated by nAChRs and intracellularly when release is evoked by mAChRs. Moreover, our data show that Aβ1-40 acts as non competitive antagonist of heteromeric α4β2* but not of α3β4* nAChRs which modulate [(3)H]NA overflow. Positive allosteric modulators of nAChRs counteract its inhibitory effect. It might be that compounds of this type could be useful to prevent, slow down the appearance or reverse the cognitive decline typical of the normal processes of brain aging.
authors: Department of Pharmacy, Section of Pharmacology and Toxicology, University of Genoa Genoa, Italy.
authors: Guendalina
authors: G
authors: Olivero
authors: Department of Pharmacy, Section of Pharmacology and Toxicology, University of Genoa Genoa, Italy.
authors: Massimo
authors: M
authors: Grilli
authors: Department of Pharmacy, Section of Pharmacology and Toxicology, University of Genoa Genoa, Italy.
authors: Jiayang
authors: J
authors: Chen
authors: Department of Drug Sciences, Centre of Excellence in Applied Biology, University of Pavia Pavia, Italy.
authors: Stefania
authors: S
authors: Preda
authors: Department of Drug Sciences, Centre of Excellence in Applied Biology, University of Pavia Pavia, Italy.
authors: Elisa
authors: E
authors: Mura
authors: Department of Drug Sciences, Centre of Excellence in Applied Biology, University of Pavia Pavia, Italy.
authors: Stefano
authors: S
authors: Govoni
authors: Department of Pharmacy, Section of Pharmacology and Toxicology, University of Genoa Genoa, Italy ; Center of Excellence for Biomedical Research, University of Genoa Genoa, Italy.
authors: Mario
authors: M
authors: Marchi
keywords: Alzheimer’s disease; beta-amyloid; dopamine release; muscarinic receptors; nicotinic receptors