AMYLOID PRECURSOR PROTEIN SECRETION VIA MUSCARINIC RECEPTORS - REDUCED DESENSITIZATION USING THE M1-SELECTIVE AGONIST AF102B

Secretion of amyloid precursor protein (APP) by cultured cells is coup led to several receptors, including mi muscarinic (m1AChR), and is ass ociated with decreased production of beta A4 amyloid. Secreted and cel l-associated APP levels were measured in m1AChR-transfected PC12 cells stimulated with the non-selective agonist carbachol or the Mi-selecti ve agonist, AF102B. Secreted APP levels following stimulation with AF1 02B (5-60 min) were about half compared with carbachol. Yet, following 24 h stimulation with carbachol or AF102B, cell-associated APP levels were similarly decreased. This may be associated with a smaller reduc tion in APP secretion following 24 h stimulation with AF102B as compar ed with carbachol. AF102B may therefore have an advantage over non-sel ective muscarinic ligands for sustained decrease of cell-associated AP P. (C) 1994 Academic Press, Inc.