NGF-dependent neurotrophic-like effects of af102b, an M1 muscarinic agonist, in PC12M1 cells

David Gurwitz, Rachel Haring, Ronit Pinkas-Kramarski, Reuben Stein, Eliahu Heldman, Yishai Karton, Abraham Fisher

Research output: Contribution to journalArticlepeer-review

Abstract

THE non-selective muscarinic agonist oxotremorine induces atropine-sensitive neurite outgrowth in PC12 cells stably transfected with ml muscarinic receptors. In contrast, AF102B, an Ml-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 phosphoinos- itide 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.

Original languageEnglish
Pages (from-to)485-488
Number of pages4
JournalNeuroReport
Volume6
Issue number3
DOIs
StatePublished - Feb 1995

Keywords

  • Acetylcholine
  • Alzheimer’s disease
  • Cyclic amp
  • Muscarinic receptor
  • Nerve growth factor
  • Neurite outgrowth
  • Pc12 cells
  • Phos- phoinositide hydrolysis

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