Neuronal to non-neuronal shift of purine resources in the tripartite myenteric synapse of postinflammatory ileitis

  • C. Vieira
    Affiliations
    Laboratório de Farmacologia e Neurobiologia, Centro de Investigação Farmacológica e Inovação Medicamentosa (MedInUP), Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, Portugal
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  • M.T. Magalhães-Cardoso
    Affiliations
    Laboratório de Farmacologia e Neurobiologia, Centro de Investigação Farmacológica e Inovação Medicamentosa (MedInUP), Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, Portugal
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  • F. Ferreirinha
    Affiliations
    Laboratório de Farmacologia e Neurobiologia, Centro de Investigação Farmacológica e Inovação Medicamentosa (MedInUP), Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, Portugal
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  • I. Silva
    Affiliations
    Laboratório de Farmacologia e Neurobiologia, Centro de Investigação Farmacológica e Inovação Medicamentosa (MedInUP), Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, Portugal
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  • A. Dias
    Affiliations
    Laboratório de Farmacologia e Neurobiologia, Centro de Investigação Farmacológica e Inovação Medicamentosa (MedInUP), Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, Portugal
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  • P. Correia-de-Sá
    Correspondence
    Corresponding author.
    Affiliations
    Laboratório de Farmacologia e Neurobiologia, Centro de Investigação Farmacológica e Inovação Medicamentosa (MedInUP), Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, Portugal
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      Purinergic signaling undergoes plastic modifications during gastrointestinal inflammation. Purines may be released from activated inflammatory cells, as well from neighboring neuronal and non-neuronal enteric cells. Here, we investigated changes in the release sites of ATP and adenosine in postinflammatory ileitis provoked in adult Wistar rats by intraluminal instillation of 2,4,6-trinitrobenzenesulfonic acid (TNBS). TNBS-treated preparations release higher amounts of ATP, while the adenosine (plus inosine) content was severely depressed (Vieira et al., 2014). Electrically-evoked ATP release increased from 2 ± 1 to 13 ± 2 fmol/mg (n = 3) in TNBS-treated preparations incubated with the nerve action potential blocker, tetrodotoxin (TTX, 1 μM). Conversely, TTX (1 μM) decreased adenosine outflow from 37 ± 6 to 20 ± 2 pmol/mg in control preparations, but it was virtually devoid of effect in TNBS-treated preparations (18 ± 3 vs 15 ± 4 pmol/mg). Results indicate that adenosine originates as such from non-neuronal sources in postinflammatory ileitis. Blockade of Cav3 (T-type) channels in interstitial cells of Cajal with mibefradil (3 μM) reduced the outflow of adenosine in control and TNBS-treated preparations to 14 ± 3 and 10 ± 3 pmol/mg, respectively. The same was verified with the nucleoside transport inhibitor, dipyridamole (0.5 μM). Neither mibefradil (3 μM) nor dipyridamole (0.5 μM) affected the release of ATP. Data suggest that the release of purines from the tripartite myenteric synapse change dramatically from neuronal to TTX-insensitive non-neuronal sources (most probably interstitial cells of Cajal) in postinflammatory ileitis, thus contributing to alterations in the purinergic neuromodulation that are characteristic of this condition. Work supported by FCT: project PEst-OE/SAU/UI215/2014 and PhD fellowship (SFRH/BD/79091/2011) to CV.
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