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In airways ATP refills sarcoplasmic reticulum via P2X smooth muscle receptors and induces contraction through P2Y epithelial receptors

  • Muscle Physiology
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Abstract

In airway smooth muscle (ASM), ATP induces a contraction associated with the increase of [Ca2+]i. Cytosolic Ca2+ is extruded to the extracellular space by the Na+/Ca2+ exchanger (NCX) in its normal mode. Some agonists activate the reverse mode of the NCX (NCXREV), inducing Ca2+ entry. We investigated whether ATP, via P2X receptors, activates the NCXREV and whether the increment in [Ca2+]i is used for contraction or for the sarcoplasmic reticulum (SR) refilling in guinea pig ASM. ATP contracted the ASM and this effect was blocked by indomethacin. Suramin and RB2 diminished the contraction induced by ATP; PPADS did not modify this response. In myocytes, ATP produces an increase in [Ca2+]i not modified by indomethacin. In tracheal strips, using simultaneous measurements, ATP induced a biphasic change in [Ca2+]i, (a Ca2+ peak followed by a plateau) accompanied by a contraction. Indomethacin or epithelium removal abolished this contraction, but not the Ca2+ peak, whereas the plateau was decreased by indomethacin. In myocytes, the ATP-induced [Ca2+]i increment was inhibited by suramin (~96%), PPADS (~40%), and RB2 (~57%). ATP augmented the NCXREV and this effect was abolished by SKF 96365 and TNP-ATP (P2X1 and P2X3 receptors antagonist). P2X1 and P2X3 receptors were corroborated by immunoblotting of ASM. NCXREV activation and ATP in the presence of RB2 favor the SR Ca2+ refilling. In tracheal rings, successive ATP stimulations were reduced with KB-R7943. Therefore, ATP: (1) indirectly promotes muscle contraction via epithelial P2Y receptors and prostaglandins release; (2) increases the [Ca2+]i through a prostaglandin-independent manner by activating P2X and P2Y receptors in smooth muscle; and (3) activates P2X1 and P2X3 receptors and the NCXREV which refills the SR.

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Acknowledgments

We acknowledge Posgrado en Ciencias Biomédicas, Facultad de Medicina, UNAM, and CONACYT for the scholarship to Edgar Flores during 10 months. This study was partly supported by a grant from CONACYT (81409 and 102013) and DGAPA-UNAM (IN201810-3) to Dr. Luis M. Montaño.

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No conflicts of interest are declared by the author(s).

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Authors and Affiliations

  1. Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, México, DF, México

    Edgar Flores-Soto, Jorge Reyes-García, Luz María García-Hernández, Alejandra Figueroa & Luis M. Montaño

  2. Departamento de Investigación en Hiperreactividad Bronquial, Instituto Nacional de Enfermedades Respiratorias, México, DF, Mexico

    Verónica Carbajal

  3. Departamento de Fibrosis Pulmonar, Instituto Nacional de Enfermedades Respiratorias, México, DF, México

    Marco Checa

  4. División de Biología Molecular, Instituto Potosino de Investigación Científica y Tecnológica, San Luis Potosí, SLP, México

    Carlos Barajas-López

  5. Departamento de Farmacología, Edificio de Investigación, sexto piso, laboratorio 3, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad Universitaria, CP 04360, México, DF, México

    Luis M. Montaño

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  1. Edgar Flores-Soto
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Correspondence to Luis M. Montaño.

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Flores-Soto, E., Carbajal, V., Reyes-García, J. et al. In airways ATP refills sarcoplasmic reticulum via P2X smooth muscle receptors and induces contraction through P2Y epithelial receptors. Pflugers Arch - Eur J Physiol 461, 261–275 (2011). https://doi.org/10.1007/s00424-010-0886-1

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  • DOI: https://doi.org/10.1007/s00424-010-0886-1

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