NGF-dependent neurotrophic-like effects of AF102B, an M1 muscarinic agonist, in PC12M1 cells.
The non-selective muscarinic agonist oxotremorine induces atropine-sensitive neurite outgrowth in PC12 cells stably transfected with m1 muscarinic receptors. In contrast, AF102B, an M1-selective muscarinic agonist, mediated minimal neurite outgrowth in these cells. In the presence of nerve growth factor (NGF) however, it induced atropine-sensitive neurite outgrowth in almost half the cell population. AF102B mediated phosphoinositide hydrolysis, but unlike carbachol, it did not stimulate cyclic AMP accumulation in these cells. These signals were not affected by NGF, indicating that they were not directly responsible for the cholinergic neurotrophic-like response. Our observations suggest that AF102B may improve neuronal responsiveness to neurotrophic factors, and thus may provide another beneficial aspect for treating Alzheimer's disease.
Gurwitz
D
D
Israel Institute for Biological Research, Ness-Ziona.
Haring
R
R
Pinkas-Kramarski
R
R
Stein
R
R
Heldman
E
E
Karton
Y
Y
Fisher
A
A
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D009414:Nerve Growth Factors / Q000494:pharmacology*; D016716:PC12 Cells; D010277:Parasympathomimetics / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology*; D051381:Rats; D013876:Thiophenes
D009414:Nerve Growth Factors; D010277:Parasympathomimetics; D011812:Quinuclidines; D013876:Thiophenes; D001285:Atropine; D002217:Carbachol; D000242:Cyclic AMP; C059240:cevimeline