Cholinergic activity modulates the survival of retinal ganglion cells in culture: the role of M1 muscarinic receptors.
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 microM carbamylcholine induced a two-fold increase in retinal ganglion cells survival. This effect was dose-dependent and mediated by M1 receptors since it could be blocked by 1 microM telenzepine (a M1 receptor antagonist) and mimicked by 200 microM oxotremorine (a M1 receptor agonist). The effect of carbamylcholine was abolished by 10 microM BAPTA-AM (an intracellular Ca2+ chelator), 30 microM dantrolene (an inhibitor of ryanodinic receptors), 500 nM H-89 (an inhibitor of PKA), 1.25 microM chelerythrine chloride (an inhibitor of PKC) and 50 microM PD-98059 (a MEK inhibitor). Treatment with 10 microM genistein (an inhibitor of tyrosine kinase), 25 microM 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 microM 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.
Pereira
S P
SP
Departamento de Neurobiologia, Programa de Neuroimunologia, Instituto de Biologia, Universidade Federal Fluminense, Caixa Postal 100180, 24001-970, RJ, Niterói, Brazil.
Medina
S V
SV
Araujo
E G
EG
D000109:Acetylcholine / Q000819:agonists / Q000031:analogs & derivatives / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000187:drug effects / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying; D051381:Rats; D011919:Rats, Inbred Strains; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D002121:Calcium Channel Blockers; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D009414:Nerve Growth Factors; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic; D002217:Carbachol; D000109:Acetylcholine; D002118:Calcium