title: 17β-Aminoestrogens induce guinea pig airway smooth muscle hyperresponsiveness through L-type Ca(2+) channels activation.
abstract: Therapy with estrogens is frequently used in menopausal women and as hormonal contraception. Because of its thrombotic effects, long term estrogen administration used in hormonal replacement therapy (HRT) and contraception could represent a health hazard. In this regard, 17β-aminoestrogens such as aminoestrol, butolame and pentolame have shown promising HRT potential, because they have a weak agonist estrogenic action and antithrombotic activity. Additionally, estrogens play a protective role in airway smooth muscle, but the effect of 17β-aminoestrogens on the airway smooth muscle has not been tested yet. In guinea pig tracheal smooth muscle pentolame and butolame induced hyperresponsiveness to histamine (His), carbachol (Cch) and KCl. Interestingly, aminoestrol did not show this effect at the highest concentration studied, it even lowered the contraction induced by Cch. The hyperresponsiveness induced by pentolame to His was abolished by nifedipine. In single tracheal myocytes, KCl induced an increment in the intracellular Ca(2+) concentration [Ca(2+)]i, pentolame also showed an increase in [Ca(2+)]i and the addition of KCl in the plateau of this rise further significantly augmented the [Ca(2+)]i response. Additionally, in patch clamp experiments pentolame increased the L-type Ca(2+) currents. Thus, 17β-aminoestrogens such as pentolame and butolame, but not aminoestrol, activate L-type Ca(2+) channel to induced hyperresponsiveness to Cch, His and KCl in guinea pig tracheal smooth muscle. Due to its lack of effect on airways and to its anticoagulant characteristics, aminoestrol seems to be the best alternative in the HRT among the 17β-aminoestrogens studied.
authors.affiliation: Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, México, DF, Mexico.
authors.forename: Edgar
authors.initials: E
authors.lastname: Flores-Soto
authors.affiliation: Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, México, DF, Mexico.
authors.forename: Inocencio
authors.initials: I
authors.lastname: Martínez-Villa
authors.affiliation: Laboratorio de Neurofarmacología, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, México, DF, Mexico.
authors.forename: Héctor
authors.initials: H
authors.lastname: Solís-Chagoyán
authors.affiliation: Departamento de Investigación en Hiperreactividad Bronquial, Instituto Nacional de Enfermedades Respiratorias, México, DF, Mexico.
authors.forename: Bettina
authors.initials: B
authors.lastname: Sommer
authors.affiliation: Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, México, DF, Mexico.
authors.forename: Cristina
authors.initials: C
authors.lastname: Lemini
authors.affiliation: Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, México, DF, Mexico. Electronic address: lmmr@unam.mx.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Montaño
mesh_terms: D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects*
chemical_list: D020746:Calcium Channels, L-Type; D004967:Estrogens; D011189:Potassium Chloride; D006632:Histamine; D002217:Carbachol
keywords: 17β-Aminoestrogens; Airway hyperresponsiveness; L-type Ca(2+) channels; Tracheal smooth muscle