Post-inflammatory Ileitis Induces Non-neuronal Purinergic Signaling Adjustments of Cholinergic Neurotransmission in the Myenteric Plexus

• Type: Article in International Scientific Journal
• Date: 2017

Authors

Vieira, C (Author) Other; Ferreirinha, F (Author) Other; Magalhaes Cardoso, MT (Author) Other; Silva, I (Author) Other; Marques, P (Author) Other; Paulo Correia de Sá (Author) ICBAS

Journal

Title: Frontiers in Pharmacology

Vol. 8

ISSN: 1663-9812

Publisher: Frontiers Media

Indexing

ISI Web of Knowledge - 0 Citations

Other information

Authenticus ID: P-00N-749

DOI: 10.3389/fphar.2017.00811

Abstract (EN): Uncoupling between ATP overflow and extracellular adenosine formation changes purinergic signaling in post-inflammatory ileitis. Adenosine neuromodulation deficits were ascribed to feed-forward inhibition of ecto-5'-nucleotidase/CD73 by high extracellular adenine nucleotides in the inflamed ileum. Here, we hypothesized that inflammation-induced changes in cellular density may also account to unbalance the release of purines and their influence on [H-3] acetylcholine release from longitudinal muscle-myenteric plexus preparations of the ileum of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-treated rats. The population of S100 beta-positive glial cells increase, whereas Ano-1-positive interstitial cells of Cajal (ICCs) diminished, in the ileum 7-days after the inflammatory insult. In the absence of changes in the density of VAChT-positive cholinergic nerves detected by immunofluorescence confocal microscopy, the inflamed myenteric plexus released smaller amounts of [H-3] acetylcholine which also became less sensitive to neuronal blockade by tetrodotoxin (1 mu M). Instead, [H-3] acetylcholine release was attenuated by sodium fluoroacetate (5 mM), carbenoxolone (10 mu M) and A438079 (3 mu M), which prevent activation of glial cells, pannexin-1 hemichannels and P2X7 receptors, respectively. Sodium fluoroacetate also decreased ATP overflow without significantly affecting the extracellular adenosine levels, thus indicating that surplus ATP release parallels reactive gliosis in post-inflammatory ileitis. Conversely, loss of ICCs may explain the lower amounts of adenosine detected in TNBS-treated preparations, since blockade of Ca(v)3 (T-type) channels existing in ICCs with mibefradil (3 mu M) or inhibition of the equilibrative nucleoside transporter 1 with dipyridamole (0.5 mu M), both decreased extracellular adenosine. Data indicate that post-inflammatory ileitis operates a shift on purinergic neuromodulation reflecting the upregulation of ATP-releasing enteric glial cells and the depletion of ICCs accounting for decreased adenosine overflow via equilibrative nucleoside transporters.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 23