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cGMP reduces the sarcoplasmic reticulum Ca2+ loading in airway smooth muscle cells: a putative mechanism in the regulation of Ca2+ by cGMP

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Abstract

Ca2+ and cGMP have opposite roles in many physiological processes likely due to a complex negative feedback regulation between them. Examples of opposite functions induced by Ca2+ and cGMP are smooth muscle contraction and relaxation, respectively. A main Ca2+ storage involved in contraction is sarcoplasmic reticulum (SR); nevertheless, the role of cGMP in the regulation of SR-Ca2+ has not been completely understood. To evaluate this role, intracellular Ca2+ concentration ([Ca2+]i) was determinated by a ratiometric method in isolated myocytes from bovine trachea incubated with Fura-2/AM. The release of Ca2+ from SR induced by caffeine was transient, whereas caffeine withdrawal was followed by a [Ca2+]i undershoot. Caffeine-induced Ca2+ transient peak and [Ca2+]i undershoot after caffeine were reproducible in the same cell. Dibutyryl cGMP (db-cGMP) blocked the [Ca2+]i undershoot and reduced the subsequent caffeine peak (SR-Ca2+ loading). Both, the opening of SR channels with ryanodine (10 μM) and the blockade of SR-Ca2+ ATPase with cyclopiazonic acid inhibited the [Ca2+]i undershoot as well as the SR-Ca2+ loading. The addition of db-cGMP to ryanodine (10 μM) incubated cells partially restored the SR-Ca2+ loading. Cyclic GMP enhanced [Ca2+]i undershoot induced by the blockade of ryanodine channels with 50 μM ryanodine. In conclusion, the reduction of SR-Ca2+ content in airway smooth muscle induced by cGMP can be explained by the combination of SR-Ca2+ loading and the simultaneous release of SR-Ca2+. The reduction of SR-Ca2+ content induced by cGMP might be a putative mechanism limiting releasable Ca2+ in response to a particular stimulus.

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  1. Departamento de Hiperreactividad Bronquial, Ismael Cosío Villegas, Instituto Nacional de Enfermedades Respiratorias, Calzada de Tlalpan 4502, Colonia Sección XVI, 14080, Mexico, DF, Mexico

    Blanca Bazán-Perkins

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  1. Blanca Bazán-Perkins
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Correspondence to Blanca Bazán-Perkins.

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Bazán-Perkins, B. cGMP reduces the sarcoplasmic reticulum Ca2+ loading in airway smooth muscle cells: a putative mechanism in the regulation of Ca2+ by cGMP. J Muscle Res Cell Motil 32, 375–382 (2012). https://doi.org/10.1007/s10974-011-9266-5

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  • DOI: https://doi.org/10.1007/s10974-011-9266-5

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