title: (+/-)3,4-Methylenedioxyamphetamine elicits action potential bursts in a central snail neuron.
abstract: The effects of (+/-)3,4-methylenedioxyamphetamine (MDA) were studied in an identifiable RP4 neuron of the African snail, Achatina fulica Ferussac, using the two-electrode voltage-clamp method. The RP4 neuron generated spontaneous action potentials. Extracellular or intracellular application of MDA elicited action potential bursts of the central RP4 neuron. The action potential bursts elicited by MDA were not blocked when neurons were immersed in high-Mg2+ solution, Ca2+-free solution, nor after continuous perfusion with atropine, d-tubocurarine, propranolol, prazosin, haloperidol, sulpiride or methiothepin. Notably, the induction of action potential bursts was blocked by pretreatment with protein kinase C (PKC) inhibitors, chelerythrine and Ro 31-8220, but not by protein kinase A (PKA) inhibitors, KT-5720 and H89, nor by the phospholipase C (PLC) inhibitor, U73122. PKC activators, i.e., phorbol 12,13-dibutyrate (PDBu) and 1-oleoyl-2-acety-sn-glycerol (OAG; a membrane-permeant DAG analog), facilitate the induction of action potential bursts elicited by MDA. Voltage-clamp studies revealed that MDA decreased the delayed rectifying K+ current (I(KD)) of the RP4 neuron. Further, although Ro 31-8220 did not affect the I(KD), Ro 31-8220 decreased the inhibitory effect of MDA on the I(KD). These results suggest that the generation of action potential bursts elicited by MDA was not due to (1) the synaptic effects of neurotransmitters, (2) the cholinergic, adrenergic, dopaminergic or serotoninergic receptors of the excitable membrane. Instead, the MDA-elicited action potential bursts are closely related to PKC activity and the inhibitory effects on the I(KD).
authors.affiliation: Department of Pharmacology, College of Medicine, National Taiwan University, No.1, Section 1, Jen-Ai Road, Taipei, Taiwan.
authors.forename: Ming-Cheng
authors.initials: MC
authors.lastname: Tsai
authors.forename: Yi-Hung
authors.initials: YH
authors.lastname: Chen
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D053119:Benzophenanthridines / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002227:Carbazoles / Q000494:pharmacology; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D017952:Ganglia, Invertebrate / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D006213:Hallucinogens / Q000494:pharmacology*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D012908:Snails / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D000470:Alkaloids; D053119:Benzophenanthridines; D002227:Carbazoles; D004791:Enzyme Inhibitors; D004963:Estrenes; D006213:Hallucinogens; D007211:Indoles; D007546:Isoquinolines; D010726:Phosphodiesterase Inhibitors; D011758:Pyrroles; D011760:Pyrrolidinones; D013449:Sulfonamides; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C057416:KT 5720; C016299:chelerythrine; D011493:Protein Kinase C; D008274:Magnesium; D018817:N-Methyl-3,4-methylenedioxyamphetamine; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; C064758:Ro 31-8220