title: Identification of a sphingosine-sensitive Ca2+ channel in the plasma membrane of Leishmania mexicana.
abstract: The disruption of the intracellular Ca(2+) homeostasis of Leishmania mexicana represents a major target for the action of drugs, such as amiodarone and miltefosine. However, little is known about the mechanism of Ca(2+) entry to these cells. Here we show the presence of a Ca(2+) channel in the plasma membrane of these parasites. This channel has many characteristics similar to the human L-type voltage-gated Ca(2+) channel. Thus, Ca(2+) entry is blocked by verapamil, nifedipine and diltiazem while Bay K 8644 opened this channel. However, different to its human counterpart, sphingosine was able to open this channel, while other well known sphingolipids had no effect. This fact could have important pharmacological implications.
authors.affiliation: Instituto de Estudios Avanzados, Caracas, Venezuela. gbenaim@idea.gob.ve
authors.forename: Gustavo
authors.initials: G
authors.lastname: Benaim
authors.forename: Yael
authors.initials: Y
authors.lastname: García-Marchán
authors.forename: Claudia
authors.initials: C
authors.lastname: Reyes
authors.forename: Graciela
authors.initials: G
authors.lastname: Uzcanga
authors.forename: Katherine
authors.initials: K
authors.lastname: Figarella
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000595:Amino Acid Sequence; D002118:Calcium / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D002518:Ceramides / Q000494:pharmacology; D006801:Humans; D007894:Leishmania mexicana / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D020539:Sequence Analysis, Protein; D013110:Sphingosine / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
chemical_list: D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D002518:Ceramides; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D014700:Verapamil; D013110:Sphingosine; D002118:Calcium