Su2046 Delayed Gastrointestinal Transit in OB/OB Mice Correlates With Reduced Intestinal TLR4 Signaling and Loss of Nitrergic Neurons

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100 μM). L-732,138 (NK1 receptor antagonist, 10 μM) or atropine (1 μM) were used to record contractions driven primarily by acetylcholine or tachykinins, respectively. In addition, contractions elicited by exogenous substance P (SP, 10 μM) or carbachol (10 μM), in the presence of tetrodotoxin (1 μM), were assessed. Electrically evoked contractile responses (5 Hz) in the presence L-NAME were also recorded and expressed as % of contractions in the absence of L-NAME. Each value represents the mean ± S.E.M obtained from 6 experiments. Results. Electrically evoked cholinergic contractions were decreased in rats sacrificed at day 28 and 56 after 6-OHDA injection (77.2±6.3 and 53.8±0.1, respectively), in comparison with controls (99±6.51). Conversely, carbachol-evoked contractions were enhanced in rats with PD both at day 28 and 56 (81.5±3.4 and 98.2±3.8, respectively), as compared to controls (52.2±5.6). Electrically evoked tachykininergic contractions were enhanced both at day 28 (85.6±5.2) and 56 (67.3±3.3), in comparison with controls (43.6±6.5). Likewise, contractions elicited by exogenous SP in colonic preparations from PD rats were also increased both at day 28 (244±11.9) and 56 (188.2±13.9), as compared to controls (79.6±6.3). In the presence of L-NAME, electrically evoked contractions in controls were enhanced (+42.3±11.9%), while they were decreased in rats at day 28 and 56 after 6-OHDA injection (+29.1±4.4% and +15±5.3%, respectively). Conclusion. Experimental PD, elicited by nigrostriatal dopaminergic degeneration, is associated with changes in neurotransmitter pathways driving colonic excitatory and inhibitory motor functions: an impairment of nitrergic and cholinergic transmission occurs in concomitance with an enhancement of tachykininergic control. Such a shift takes place along with an up-regulation of the contractile responses mediated bymuscarinic receptors on smoothmuscle, whichmight be compensatory in nature.