title: Melatonin antagonizes apoptosis via receptor interaction in U937 monocytic cells.
abstract: Among the non-neurological functions of melatonin, much attention is being directed to the ability of melatonin to modulate the immune system, whose cells possess melatonin-specific receptors and biosynthetic enzymes. Melatonin controls cell behaviour by eliciting specific signal transduction actions after its interaction with plasma membrane receptors (MT(1), MT(2)); additionally, melatonin potently neutralizes free radicals. Melatonin regulates immune cell loss by antagonizing apoptosis. A major unsolved question is whether this is due to receptor involvement, or to radical scavenging considering that apoptosis is often dependent on oxidative alterations. Here, we provide evidence that on U937 monocytic cells, apoptosis is antagonized by melatonin by receptor interaction rather than by radical scavenging. First, melatonin and a set of synthetic analogues prevented apoptosis in a manner that is proportional to their affinity for plasma membrane receptors but not to their antioxidant ability. Secondly, melatonin's antiapoptotic effect required key signal transduction events including G protein, phospholipase C and Ca(2+) influx and, more important, it is sensitive to the specific melatonin receptor antagonist luzindole.
authors.affiliation: Dipartimento di Biologia, Università di Roma Tor Vergata, Rome, Italy.
authors.forename: Flavia
authors.initials: F
authors.lastname: Radogna
authors.forename: Laura
authors.initials: L
authors.lastname: Paternoster
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Albertini
authors.forename: Claudia
authors.initials: C
authors.lastname: Cerella
authors.forename: Augusto
authors.initials: A
authors.lastname: Accorsi
authors.forename: Anahi
authors.initials: A
authors.lastname: Bucchini
authors.forename: Gilberto
authors.initials: G
authors.lastname: Spadoni
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Diamantini
authors.forename: Giorgio
authors.initials: G
authors.lastname: Tarzia
authors.forename: Milena
authors.initials: M
authors.lastname: De Nicola
authors.forename: Maria
authors.initials: M
authors.lastname: D'Alessio
authors.forename: Lina
authors.initials: L
authors.lastname: Ghibelli
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects; D006801:Humans; D008550:Melatonin / Q000031:analogs & derivatives / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D037342:Pertussis Toxin / Q000494:pharmacology; D044094:Receptors, Melatonin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014363:Tryptamines / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism; D020298:U937 Cells
chemical_list: D044094:Receptors, Melatonin; D014363:Tryptamines; C057154:luzindole; D037342:Pertussis Toxin; D010738:Type C Phospholipases; D008550:Melatonin; D002118:Calcium