Differential modulation of carbachol and trans-ACPD-stimulated phosphoinositide turnover following traumatic brain injury.
In the fluid percussion model of traumatic brain injury (TBI), we examined muscarinic and metabotropic glutamate receptor-stimulated polyphosphoinositide (PPI) turnover in rat hippocampus. Moderate injury was obtained by displacement and deformation of the brain within the closed cranial cavity using a fluid percussion device. Carbachol and (+/-)-1-Aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD)-stimulated PPI hydrolysis was assayed in hippocampus from injured and sham-injured controls at both 1 hour and 15 days following injury. At 1 hour after TBI, the response to carbachol was enhanced in injured rats by up to 200% but the response to trans-ACPD was diminished by as much as 28%. By contrast, at 15 days after TBI, the response to carbachol was enhanced by 25% and the response to trans-ACPD was enhanced by 73%. The ionotropic glutamate agonists N-methyl-D-aspartate (NMDA), and alpha-amino-3 hydroxy-5-methyl-4-isoxazolepropionate (AMPA), did not increase PPI hydrolysis in either sham or injured rats and injury did not alter basal hydrolysis. Thus, hippocampal muscarinic and metabotropic receptors linked to phospholipase C are differentially altered by TBI.
Delahunty
T M
TM
Department of Surgery Medical College of Virginia/Virginia Commonwealth University, Richmond 23298-0693, USA.
Jiang
J Y
JY
Black
R T
RT
Lyeth
B G
BG
D000818:Animals; D001930:Brain Injuries / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology*; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D009498:Neurotoxins / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical
D009498:Neurotoxins; D010716:Phosphatidylinositols; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D002217:Carbachol