title: Phorbol ester modulation of both delta-mutant and subunit-omitted nicotinic receptors expressed in Xenopus oocytes.
abstract: The action of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), the potent stimulator of protein kinase C (PKC), on acetylcholine-activated currents (I(Ach)) was investigated in voltage clamped Xenopus laevis oocytes injected with RNAs encoding murine embryonic nicotinic acetylcholine receptor (AChR) subunits. Comparable potentiation and acceleration of decay of I(ACh) were observed within minutes of phorbol ester application in oocytes injected with various RNA subunit combinations: (i) alpha beta gamma delta; (ii) alpha beta gamma; (iii) alpha beta delta; and (iv) alpha beta gamma delta(AAA), a mutant of the delta subunit with serine residues 360-361-362 mutated to alanine. Our findings indicate that the effects on I(ACh) induced by PKC stimulation are independent of both gamma and delta subunits and, accordingly, of the presence of PKC phosphorylation sites on delta subunit. It is here suggested a novel PKC-dependent modulatory mechanism of cholinergic receptor which does not involve direct phosphorylation of the AChR and requires phosphorylation of intermediate regulatory protein(s).
authors.affiliation: Laboratorio di Biofisica, Centro Ricerca Sperimentale, Istituto Regina Elena, Roma, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Limatola
authors.forename: E
authors.initials: E
authors.lastname: Palma
authors.forename: A M
authors.initials: AM
authors.lastname: Mileo
authors.forename: F
authors.initials: F
authors.lastname: Eusebi
mesh_terms: D000818:Animals; D009154:Mutation / Q000187:drug effects*; D009865:Oocytes / Q000187:drug effects*; D010703:Phorbol Esters / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000187:drug effects*; D014981:Xenopus
chemical_list: D010703:Phorbol Esters; D011978:Receptors, Nicotinic