title: The effect of centrally injected CDP-choline on respiratory system; involvement of phospholipase to thromboxane signaling pathway.
abstract: CDP-choline is an endogenous metabolite in phosphatidylcholine biosynthesis. Exogenous administration of CDP-choline has been shown to affect brain metabolism and to exhibit cardiovascular, neuroendocrine neuroprotective actions. On the other hand, little is known regarding its respiratory actions and/or central mechanism of its respiratory effect. Therefore the current study was designed to investigate the possible effects of centrally injected CDP-choline on respiratory system and the mediation of the central cholinergic receptors and phospholipase to thromboxane signaling pathway on CDP-choline-induced respiratory effects in anaesthetized rats. Intracerebroventricularly (i.c.v.) administration of CDP-choline induced dose- and time-dependent increased respiratory rates, tidal volume and minute ventilation of male anaesthetized Spraque Dawley rats. İ.c.v. pretreatment with atropine failed to alter the hyperventilation responses to CDP-choline whereas mecamylamine, cholinergic nicotinic receptor antagonist, mepacrine, phospholipase A2 inhibitor, and neomycin phospholipase C inhibitor, blocked completely the hyperventilation induced by CDP-choline. In addition, central pretreatment with furegrelate, thromboxane A2 synthesis inhibitor, also partially blocked CDP-choline-evoked hyperventilation effects. These data show that centrally administered CDP-choline induces hyperventilation which is mediated by activation of central nicotinic receptors and phospholipase to thromboxane signaling pathway.
authors.affiliation: Department of Physiology, Faculty of Veterinary Medicine, Uludag University, Bursa 16059, Turkey.
authors.forename: Bora B
authors.initials: BB
authors.lastname: Topuz
authors.affiliation: Department of Physiology, Faculty of Veterinary Medicine, Uludag University, Bursa 16059, Turkey.
authors.forename: Burcin
authors.initials: B
authors.lastname: Altinbas
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Uludag University, Bursa 16059, Turkey.
authors.forename: Mustafa S
authors.initials: MS
authors.lastname: Yilmaz
authors.affiliation: Division of Cardiovascular and Diabetes Research, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Sikha
authors.initials: S
authors.lastname: Saha
authors.affiliation: Division of Cardiovascular and Diabetes Research, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Trevor F
authors.initials: TF
authors.lastname: Batten
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Uludag University, Bursa 16059, Turkey.
authors.forename: Vahide
authors.initials: V
authors.lastname: Savci
authors.affiliation: Department of Physiology, Faculty of Veterinary Medicine, Uludag University, Bursa 16059, Turkey. Electronic address: muraty@uludag.edu.tr.
authors.forename: Murat
authors.initials: M
authors.lastname: Yalcin
mesh_terms: D000818:Animals; D003566:Cytidine Diphosphate Choline / Q000008:administration & dosage* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006985:Hyperventilation / Q000139:chemically induced* / Q000503:physiopathology*; D007276:Injections, Intraventricular; D008297:Male; D010740:Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D056152:Respiratory Rate / Q000187:drug effects; D019141:Respiratory System Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015398:Signal Transduction; D013931:Thromboxanes / Q000378:metabolism*; D013990:Tidal Volume / Q000187:drug effects; D013997:Time Factors
chemical_list: D019141:Respiratory System Agents; D013931:Thromboxanes; D003566:Cytidine Diphosphate Choline; D010740:Phospholipases
keywords: CDP-choline; Central cholinergic receptors; Central prostaglandinergic system; Intracerebroventricular; Minute ventilation; Respiratory frequency; Tidal volume