title: The anti-inflammatory drug celecoxib inhibits T-type Ca2+ currents in spermatogenic cells yet it elicits the acrosome reaction in mature sperm.
abstract: Celecoxib (Cx), an anti-inflammatory drug designed to inhibit COX2, can affect some ion channels. T-type (CaV3) channels have been implicated in sperm physiology. Here we report and characterize the Cx induced inhibition of T-type channels in mouse spermatogenic cells. Unexpectedly, Cx can also induce the acrosome reaction (AR), an intracellular Ca(2+) ([Ca(2+)]i) increase and a sperm depolarization. This [Ca(2+)]i increase possibly results from the ability Cx has to alkalinize intracellular pH (pHi), which is known to activate the sperm specific Ca(2+) channel CatSper. As the Cx induced [Ca(2+)]i increase is sensitive to mibefradil, a CatSper blocker, this channel may mediate the Cx-induced Ca(2+) entry leading to the AR. Our observations demonstrate that Cx can compromise fertilization.
authors.affiliation: Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Avenida Universidad 2001, Col. Chamilpa, C.P. 62210 Cuernavaca Mor., Mexico.
authors.forename: E
authors.initials: E
authors.lastname: Balderas
authors.forename: C
authors.initials: C
authors.lastname: Sánchez-Cárdenas
authors.forename: J C
authors.initials: JC
authors.lastname: Chávez
authors.forename: J L
authors.initials: JL
authors.lastname: de la Vega Beltrán
authors.forename: F
authors.initials: F
authors.lastname: Gómez-Lagunas
authors.forename: C L
authors.initials: CL
authors.lastname: Treviño
authors.forename: A
authors.initials: A
authors.lastname: Darszon
mesh_terms: D020101:Acrosome Reaction / Q000187:drug effects*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D020747:Calcium Channels, T-Type / Q000187:drug effects*; D000068579:Celecoxib; D008297:Male; D051379:Mice; D011720:Pyrazoles / Q000494:pharmacology*; D013091:Spermatogenesis / Q000187:drug effects*; D013094:Spermatozoa / Q000187:drug effects*; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D020747:Calcium Channels, T-Type; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib
keywords: Acrosome reaction; Anti-inflammatory drug; Celecoxib; Fertilization; T-type channel