title: Testosterone-induced relaxation involves L-type and store-operated Ca2+ channels blockade, and PGE 2 in guinea pig airway smooth muscle.
abstract: In vascular smooth muscle, it has been described that testosterone (TES) produces relaxation by blocking L-type Ca(2+) channels. Recently, we found that L-type Ca(2+) and store-operated Ca(2+) (SOC) channels are the main membranal structures that provide extracellular Ca(2+) for carbachol (CCh)-induced contraction in airway smooth muscle (ASM). We studied the possible interactions between L-type and SOC channels in TES-induced relaxation in guinea pig ASM. TES (10, 32, 100, and 178 μM) induced a complete relaxation of CCh-precontracted tracheal smooth muscle, and indomethacin partially inhibited this response. In single myocytes, the KCl-induced intracellular Ca(2+) increase ([Ca(2+)]i) was decreased by 32 and completely blocked by 100 nM TES. This androgen (32 and 100 μM) significantly diminished (~25 and 49 %, respectively) the capacitative Ca(2+) entry. Myocytes stimulated with CCh produced a transient Ca(2+) peak followed by a sustained plateau. D-600 was added during the plateau phase, and a partial diminution (~35 %) was observed. A greater decrease (~78 %) was seen when 2-aminoethyl diphenylborinate (2-APB, SOC antagonist) was used. The combination of both drugs completely abolished the Ca(2+) plateau induced by CCh. TES (100 μM) also completely abolished the CCh-induced Ca(2+) plateau. Indomethacin significantly diminished this effect of TES. PGE2 and butaprost proportionally decreased the Ca(2+) plateau as indomethacin blocked it. Sarcoplasmic reticulum refilling was partially, dependently, and significantly diminished by TES. We concluded that TES-induced relaxation involves blockade of L-type Ca(2+) channels at nanomolar and SOC channels at micromolar concentration and PGE2 seems to be also involved in this phenomenon.
authors.affiliation: Departamento de Biología Celular y Fisiología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México, DF, México.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Perusquía
authors.forename: Edgar
authors.initials: E
authors.lastname: Flores-Soto
authors.forename: Bettina
authors.initials: B
authors.lastname: Sommer
authors.forename: Elias
authors.initials: E
authors.lastname: Campuzano-González
authors.forename: Inocencio
authors.initials: I
authors.lastname: Martínez-Villa
authors.forename: Aldo I
authors.initials: AI
authors.lastname: Martínez-Banderas
authors.forename: Luis M
authors.initials: LM
authors.lastname: Montaño
mesh_terms: D000527:Alprostadil / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism; D020013:Calcium Signaling; D002478:Cells, Cultured; D015232:Dinoprostone / Q000494:pharmacology*; D006168:Guinea Pigs; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D013739:Testosterone / Q000494:pharmacology*; D014132:Trachea / Q000166:cytology / Q000378:metabolism* / Q000502:physiology
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D013739:Testosterone; D000527:Alprostadil; C048491:butaprost; D015232:Dinoprostone; D007213:Indomethacin