PMID- 24704528
OWN - NLM
STAT- MEDLINE
DCOM- 20141208
LR  - 20140430
IS  - 1872-6240 (Electronic)
IS  - 0006-8993 (Linking)
VI  - 1563
DP  - 2014 May 14
TI  - Centrally administered CDP-choline induced cardiovascular responses are mediated 
      by activation of the central phospholipase-prostaglandin signaling cascade.
PG  - 61-71
LID - S0006-8993(14)00418-1 [pii]
LID - 10.1016/j.brainres.2014.03.040 [doi]
AB  - The present study was designed to determine the involvement of central 
      prostaglandin synthesis on the pressor and bradycardic effect of cytidine 
      5'-diphosphocholine (CDP-choline). Intracerebroventricular (i.c.v.) 
      administration of CDP-choline was made and blood pressure and heart rate were 
      recorded in male Sprague Dawley rats throughout this study. Microdialysis and 
      immunohistochemical studies were performed to measure extracellular total 
      prostaglandin concentration and to show cyclooxygenase-1 and -2 (COX-1 and -2) 
      immunoreactivities, respectively, in the posterior hypothalamic area. Moreover, 
      rats were pretreated (i.c.v) with mepacrine [a phospholipase A2 (PLA2) 
      inhibitor], ibuprofen [a nonselective COX inhibitor], neomycine [a phospholipase 
      C (PLC) inhibitor] or furegrelate [a thromboxane A2 (TXA2) synthesis inhibitor] 5 
      min prior to the injection of CDP-choline to determine the effects of these 
      inhibitors on cardiovascular responses to CDP-choline. Control rats were 
      pretreated (i.c.v) with saline. CDP-choline caused a dose- and time-dependent 
      increase in blood pressure and decrease in heart rate. Immunohistochemical 
      studies showed that CDP-choline increased COX-1 and -2 immunoreactivities in the 
      posterior hypothalamic area. CDP-choline also elevated hypothalamic extracellular 
      total prostaglandin concentration by 62%, as shown in microdialysis studies. 
      Mepacrine or ibuprofen pretreatments almost completely blocked the pressor and 
      bradycardic responses to CDP-choline while neomycine or furegrelate partially 
      attenuated the drug-induced cardiovascular effects. The results suggest that 
      CDP-choline may stimulate prostaglandin synthesis through the activation of PLA2, 
      cyclooxygenases (COX-1 and -2) and prostaglandins and at least TXA2, may mediate 
      the drug׳s cardiovascular effects.
CI  - Copyright (c) 2014 Elsevier B.V. All rights reserved.
FAU - Topuz, Bora B
AU  - Topuz BB
AD  - Department of Physiology, Faculty of Veterinary Medicine, Uludag University, 
      Bursa 16059, Turkey.
FAU - Altinbas, Burcin
AU  - Altinbas B
AD  - Department of Physiology, Faculty of Veterinary Medicine, Uludag University, 
      Bursa 16059, Turkey.
FAU - Ilhan, Tuncay
AU  - Ilhan T
AD  - Department of Histology and Embryology, Faculty of Veterinary Medicine, Uludag 
      University, Bursa 16059, Turkey.
FAU - Yilmaz, Mustafa S
AU  - Yilmaz MS
AD  - Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Uludag 
      University, Bursa 16059, Turkey.
FAU - Erdost, Hatice
AU  - Erdost H
AD  - Department of Histology and Embryology, Faculty of Veterinary Medicine, Uludag 
      University, Bursa 16059, Turkey.
FAU - Saha, Sikha
AU  - Saha S
AD  - Division of Cardiovascular and Diabetes Research, Leeds Institute of Genetics, 
      Health and Therapeutics, University of Leeds, Leeds LS2 9JT, UK.
FAU - Savci, Vahide
AU  - Savci V
AD  - Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Uludag 
      University, Bursa 16059, Turkey.
FAU - Yalcin, Murat
AU  - Yalcin M
AD  - Department of Physiology, Faculty of Veterinary Medicine, Uludag University, 
      Bursa 16059, Turkey. Electronic address: mrtylcn75@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140402
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Prostaglandins)
RN  - 536BQ2JVC7 (Cytidine Diphosphate Choline)
RN  - EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthases)
RN  - EC 3.1.- (Phospholipases)
SB  - IM
MH  - Animals
MH  - Blood Pressure/drug effects
MH  - Cytidine Diphosphate Choline/administration & dosage/*pharmacology
MH  - Heart Rate/drug effects
MH  - Hypothalamus/*drug effects/*enzymology
MH  - Male
MH  - Phospholipases/*metabolism
MH  - Prostaglandin-Endoperoxide Synthases/*metabolism
MH  - Prostaglandins/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction
OTO - NOTNLM
OT  - Blood pressure
OT  - CDP-choline
OT  - Cyclooxygenase
OT  - Heart rate
OT  - Immunohistochemistry
OT  - Microdialysis
OT  - Phopspholipase A(2)
OT  - Phopspholipase C
OT  - Prostaglandins
EDAT- 2014/04/08 06:00
MHDA- 2014/12/15 06:00
CRDT- 2014/04/08 06:00
PHST- 2014/01/04 00:00 [received]
PHST- 2014/03/21 00:00 [revised]
PHST- 2014/03/28 00:00 [accepted]
PHST- 2014/04/08 06:00 [entrez]
PHST- 2014/04/08 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
AID - S0006-8993(14)00418-1 [pii]
AID - 10.1016/j.brainres.2014.03.040 [doi]
PST - ppublish
SO  - Brain Res. 2014 May 14;1563:61-71. doi: 10.1016/j.brainres.2014.03.040. Epub 2014 
      Apr 2.