PMID- 16962568
OWN - NLM
STAT- MEDLINE
DCOM- 20070123
LR  - 20181201
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 1118
IP  - 1
DP  - 2006 Nov 6
TI  - Activation of the central cholinergic system mediates the reversal of hypotension 
      by centrally administrated U-46619, a thromboxane A2 analog, in hemorrhaged rats.
PG  - 43-51
AB  - In the present study, we investigated the role of the central cholinergic system 
      in mediating the pressor effect of intracerebroventricularly administrated 
      U-46619, a thromboxane A2 (TxA2) analog, in hemorrhaged hypotensive rats. 
      Hemorrhage was performed by withdrawing a total volume of 2.1 ml of blood per 100 
      g body weight over a period of 10 min. Intracerebroventricular (i.c.v.) injection 
      of U-46619 (0.5, 1, 2 micro g) produced a dose- and time-dependent increase in 
      arterial pressure and reversed the hypotension of this condition. Hemorrhage 
      caused small increases in extracellular hypothalamic acetylcholine and choline 
      levels. Intracerebroventricular administration of U-46619 (1 micro g) further 
      increased the levels of extracellular acetylcholine and choline by 57% and 41%, 
      respectively. Pretreatment with SQ-29548 (8 mug; i.c.v.), a selective TxA2 
      receptor antagonist, completely abrogated the effects of subsequent injection of 
      U-46619 (1 mug; i.c.v.) on arterial pressure and extracellular acetylcholine and 
      choline levels. Pretreatment with mecamylamine (50 micro g; i.c.v.), a 
      cholinergic nonselective nicotinic receptor antagonist, attenuated the pressor 
      effect of U-46619 (1 micro g, i.c.v.) in hemorrhaged rats whereas pretreatment 
      with atropine (10 micro g; i.c.v.), a cholinergic nonselective muscarinic 
      receptor antagonist, had no effect. Interestingly, pretreatment of rats with 
      methyllycaconitine (10 micro g; i.c.v.) or alpha-bungarotoxin (10 micro g; 
      i.c.v.), selective antagonists of alpha-7 subtype nicotinic acetylcholine 
      receptors (alpha7nAChRs), partially abolished the pressor effect of U-46619 (1 
      micro g; i.c.v.) in the hypotensive condition. Pretreatment with a combination of 
      mecamylamine plus methyllycaconitine or mecamylamine plus alpha-bungarotoxin 
      attenuated the reversal effect of U-46619, but only to the same extent as 
      pretreatment with either antagonist alone. In conclusion, i.c.v. administration 
      of U-46619 restores arterial pressure and increases posterior hypothalamic 
      acetylcholine and choline levels by activating central TxA2 receptors in 
      hemorrhaged hypotensive rats. The activation of central nicotinic cholinergic 
      receptors, predominantly alpha7nAChRs, partially acts as a mediator in the 
      pressor responses to i.c.v. injection of U-46619 under these conditions.
FAU - Yalcin, Murat
AU  - Yalcin M
AD  - Uludag University Veterinary Faculty, Department of Physiology, 16059, Gorukle, 
      Bursa, Turkey.
FAU - Cavun, Sinan
AU  - Cavun S
FAU - Yilmaz, M Sertac
AU  - Yilmaz MS
FAU - Savci, Vahide
AU  - Savci V
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060908
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Bridged Bicyclo Compounds, Heterocyclic)
RN  - 0 (Chrna7 protein, rat)
RN  - 0 (Fatty Acids, Unsaturated)
RN  - 0 (Hydrazines)
RN  - 0 (Nicotinic Antagonists)
RN  - 0 (Receptors, Nicotinic)
RN  - 0 (Receptors, Thromboxane A2, Prostaglandin H2)
RN  - 0 (Vasoconstrictor Agents)
RN  - 0 (alpha7 Nicotinic Acetylcholine Receptor)
RN  - 57576-52-0 (Thromboxane A2)
RN  - 76898-47-0 (15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid)
RN  - 88SD2J5ZNX (SQ 29548)
RN  - N9YNS0M02X (Acetylcholine)
SB  - IM
MH  - 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid/*pharmacology
MH  - Acetylcholine/metabolism
MH  - Animals
MH  - Blood Pressure/drug effects/physiology
MH  - Bridged Bicyclo Compounds, Heterocyclic
MH  - Cholinergic Fibers/*drug effects/metabolism
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Extracellular Fluid/drug effects/metabolism
MH  - Fatty Acids, Unsaturated
MH  - Hemorrhage/complications/physiopathology
MH  - Hydrazines/pharmacology
MH  - Hypotension/*drug therapy/etiology/physiopathology
MH  - Hypothalamus, Posterior/*drug effects/metabolism
MH  - Injections, Intraventricular
MH  - Male
MH  - Neural Pathways/*drug effects/metabolism
MH  - Nicotinic Antagonists/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Nicotinic/drug effects/metabolism
MH  - Receptors, Thromboxane A2, Prostaglandin H2/antagonists & inhibitors/metabolism
MH  - Thromboxane A2/*analogs & derivatives
MH  - Time Factors
MH  - Vasoconstrictor Agents/pharmacology
MH  - alpha7 Nicotinic Acetylcholine Receptor
EDAT- 2006/09/12 09:00
MHDA- 2007/01/24 09:00
CRDT- 2006/09/12 09:00
PHST- 2006/02/24 00:00 [received]
PHST- 2006/07/31 00:00 [revised]
PHST- 2006/08/04 00:00 [accepted]
PHST- 2006/09/12 09:00 [pubmed]
PHST- 2007/01/24 09:00 [medline]
PHST- 2006/09/12 09:00 [entrez]
AID - S0006-8993(06)02369-9 [pii]
AID - 10.1016/j.brainres.2006.08.014 [doi]
PST - ppublish
SO  - Brain Res. 2006 Nov 6;1118(1):43-51. doi: 10.1016/j.brainres.2006.08.014. Epub 
      2006 Sep 8.