Title: Generalized loss of inhibitory innervation reverses serotonergic inhibition into excitation in a rabbit model of TNBS-colitis
Authors: Depoortere, Inge ×
Van Thuyne, Thijs
Peeters, TL #
Issue Date: Apr-2002
Publisher: Nature publishing group
Series Title: British Journal of Pharmacology vol:135 issue:8 pages:2011-2019
Abstract: 1. Inflammation may affect subpopulations of neurons of the myenteric plexus. 2. In the present study the effect of trinitrobenzene sulphonic acid (TNBS) induced colitis on nitrergic, purinergic and adrenergic inhibitory neurotransmission was studied as well as the consequences of the related changes on the response of 5-HT agonists using these neurotransmitters to mediate their effect. 3. Strips from normal and colitis rabbits (135 mg kg(-1) TNBS) were subjected to electrical field stimulation (EFS, 0.3 ms, 6V, 0.5 - 32 Hz, 10 s train). The response was measured isometrically in the absence or presence of L-NAME, suramin, guanethidine, the 5-HT agonists (5-HT(1/5A/7): 5-carboxamidotryptamine (5-CT), 5-HT(2): alpha-methyl-5-HT, 5-HT(3): 2-methyl-5-HT, 5-HT(4): 5-methoxytryptamine (5-MeOT)) or a combination. 4. In normal strips L-NAME (1 - 32 Hz), suramin (0.5 - 2, 8 Hz) and guanethidine (4, 16, 32 Hz) increased the response to EFS. This effect was abolished in inflamed strips and was accompanied by a decrease in nNOS expression. 5. In normal strips all 5-HT agonists induced pronounced (5-CT, alpha-methyl-5-HT) or small (2-methyl-5-HT, 5-MeOT) inhibitory neural responses. In inflamed strips this was reversed to cholinergic excitatory responses. 6. The effect of inflammation on the 5-HT(4) response was mimicked by preincubation of normal strips with L-NAME or suramin. Accordingly, in inflamed strips L-NAME or suramin did not affect the excitatory effects of 5-MeOT. 7. TNBS-colitis abolishes nitrergic, purinergic and adrenergic neurotransmission. This reverses serotonergic inhibition into excitation.
ISSN: 0007-1188
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Translational Research in GastroIntestinal Disorders
× corresponding author
# (joint) last author

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