TrkA antagonists decrease NGF-induced ChAT activity in vitro and modulate cholinergic synaptic number in vivo.
Cholinergic neurons are known to respond in vivo to the administration of nerve growth factor (NGF) by a prominent and selective increase of choline acetyl transferase activity and by cholinergic synaptogenesis in the rat brain. By using a synthetic TrkA antagonist we demonstrated that endogenously produced NGF is involved in the continual re-modeling of cholinergic neuronal connections during adulthood, acting through TrkA receptors.
Debeir
T
T
Department of Pharmacology & Therapeutics, McGill University, Montreal, PQ, Canada.
Saragovi
H U
HU
Cuello
A C
AC
D000109:Acetylcholine / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000096:biosynthesis*; D004790:Enzyme Induction; D009414:Nerve Growth Factors / Q000502:physiology*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D017729:Presynaptic Terminals / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000037:antagonists & inhibitors*; D013569:Synapses / Q000187:drug effects*
D009414:Nerve Growth Factors; D010456:Peptides, Cyclic; D011518:Proto-Oncogene Proteins; D017475:Receptors, Nerve Growth Factor; C116392:cyclic peptide 92-96C; D002795:Choline O-Acetyltransferase; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA; D000109:Acetylcholine