Premium
Cholinergic activity modulates the survival of retinal ganglion cells in culture: the role of M 1 muscarinic receptors
Author(s) -
Pereira S.P.F.,
Medina S.V.,
Araujo E.G.
Publication year - 2001
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/s0736-5748(01)00043-0
Subject(s) - oxotremorine , chelerythrine , muscarinic acetylcholine receptor , endocrinology , protein kinase c , biology , receptor antagonist , chemistry , medicine , receptor , pharmacology , microbiology and biotechnology , antagonist , kinase , biochemistry
The control of natural cell death is mediated by neurotrophins released by target, afferent and glial cells. In the present work we show that treatment of retinal cells ‘in vitro’ for 48 h with 25 μM carbamylcholine induced a two‐fold increase in retinal ganglion cells survival. This effect was dose‐dependent and mediated by M 1 receptors since it could be blocked by 1 μM telenzepine (a M 1 receptor antagonist) and mimicked by 200 μM oxotremorine (a M 1 receptor agonist). The effect of carbamylcholine was abolished by 10 μM BAPTA‐AM (an intracellular Ca 2+ chelator), 30 μM dantrolene (an inhibitor of ryanodinic receptors), 500 nM H‐89 (an inhibitor of PKA), 1.25 μM chelerythrine chloride (an inhibitor of PKC) and 50 μM PD‐98059 (a MEK inhibitor). Treatment with 10 μM genistein (an inhibitor of tyrosine kinase), 25 μM LY‐294002 (a PI‐3 kinase blocker), 30 nM brefeldin‐A (a blocker of polypeptides release), 50 nM K‐252a (a Trk receptor inhibitor) and 20 μM fluorodeoxyuridine (an inhibitor of cell proliferation) totally inhibited the effect of carbamylcholine. Taken together our results indicate that muscarinic activity controls the survival of retinal ganglion cells through a mechanism involving the release of polypeptides and activation of Irk receptors.