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CDP-choline-induced contractions in the mouse gastric fundus through purinoceptors and Rho/Rho-kinase signalling

Authors
Journal
Life Sciences
0024-3205
Publisher
Elsevier
Publication Date
Volume
88
Identifiers
DOI: 10.1016/j.lfs.2011.01.002
Keywords
  • Cdp-Choline
  • Gastric Fundus
  • Purinoceptors
  • Rho-Kinase
  • Y-27632
Disciplines
  • Biology

Abstract

Abstract Aims This study aimed to investigate the effects of cytidine-5′-diphosphocholine (CDP-choline), an endogenous lipid precursor, on the reactivity of the mouse gastric fundus and to determine the mechanism(s) mediating its effects. Main methods Possible contractile effect of CDP-choline (10 − 5 –10 − 2 M) was investigated in the absence and presence of a muscarinic receptor antagonist, atropine (3 × 10 − 6 M), an acetylcholine esterase inhibitor, physostigmine (10 − 6 M), a Na + channel blocker, tetrodotoxin (TTX, 3 × 10 − 6 M), a Rho-kinase inhibitor, Y-27632 (10 − 5 M), a purinoceptor antagonist, suramin (2 × 10 − 4 M), a nitric oxide synthase inhibitor, N G-nitro-L-arginine (L-NA, 3 × 10 − 4 M), a Ca 2+ channel blocker, nifedipine (10 − 6 M), an α 7 nicotinic receptor antagonist, methyllycaconitine citrate (MLA, 10 − 6 M) and a G protein (G i/o) inhibitor, pertussis toxin (PTX, 2 μg/ml). The metabolites of CDP-choline, namely choline (10 − 4 –10 − 2 M), cytidine 5′-triphosphate (CTP, 10 − 5 –10 − 2 M), cytidine (10 − 5 –10 − 2 M) and cytidine monophosphate (CMP, 10 − 3 –10 − 2 M) were also tested. Besides, phosphorylation of MYPT1, which indicates Rho-kinase activity, was also detected. Key findings CDP-choline produced contractions in a concentration-dependent manner. The contractions were not affected by atropine, physostigmine, TTX, PTX, MLA or L-NA. However, Y-27632, suramin or nifedipine partly reduced these contractions. CDP-choline increased phosphorylation of MYPT1. Among CDP-choline metabolites, cytidine had no contractile effects. However, choline induced considerable contractions, which were sensitive to atropine. CMP and CTP had also contractile activity, comparable to that of CDP-choline. Significance These results suggest that CDP-choline produced contraction through, at least in part, purinoceptors and Rho/Rho-kinase signalling in the mouse gastric fundus.

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