title: CDP-choline-induced contractions in the mouse gastric fundus through purinoceptors and Rho/Rho-kinase signalling.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  These results suggest that CDP-choline produced contraction through, at least in part, purinoceptors and Rho/Rho-kinase signalling in the mouse gastric fundus.
authors.affiliation: Department of Pharmacology, Medical Faculty Mersin University, Campus Yenisehir, 33169, Mersin, Turkey.
authors.forename: Ozge
authors.initials: O
authors.lastname: Guldali
authors.forename: Vahide
authors.initials: V
authors.lastname: Savci
authors.forename: Kansu
authors.initials: K
authors.lastname: Buyukafsar
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003566:Cytidine Diphosphate Choline / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005748:Gastric Fundus / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D058914:Purinergic Antagonists / Q000494:pharmacology; D011983:Receptors, Purinergic / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D058914:Purinergic Antagonists; D011983:Receptors, Purinergic; D003566:Cytidine Diphosphate Choline; D054460:rho-Associated Kinases