Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2551806 | Life Sciences | 2011 | 7 Pages |
AimsThis 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 methodsPossible 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, NG-nitro-L-arginine (L-NA, 3 × 10− 4 M), a Ca2+ channel blocker, nifedipine (10− 6 M), an α7 nicotinic receptor antagonist, methyllycaconitine citrate (MLA, 10− 6 M) and a G protein (Gi/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 findingsCDP-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.SignificanceThese results suggest that CDP-choline produced contraction through, at least in part, purinoceptors and Rho/Rho-kinase signalling in the mouse gastric fundus.