Early changes in second messenger but not receptor binding sites after acute subdural hematoma: an in vitro autoradiographic study.
Neurotransmitter receptor-coupled mechanisms have been recently recognized as important determinants of cell damage after central nervous system (CNS) trauma and ischemia. Many of these receptors exert their intracellular effects via second messenger systems. This study used in vitro autoradiographic radioligand binding to measure beta-adrenergic and muscarinic cholinergic receptors and adenylate cyclase and protein kinase C (PKC) binding sites two h after acute subdural hematoma in rats. Both beta-adrenergic and cholinergic receptor binding sites were unchanged in comparison to controls, while adenylate cyclase binding significantly decreased in the ischemic cortex under the hematoma. These changes may constitute a major limiting factor on receptor-linked therapeutic strategies in trauma and ischemia. Protein kinase C activation significantly increased in the ischemic area under the hematoma in these studies. This appears to be a response to calcium flux, which may be in part glutamate mediated.
Department of Neurosurgery, University of Glasgow, Scotland.
Y
Y
Kuroda
D
D
Dewar
R
R
Bullock
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D001784:Blood Gas Analysis; D001930:Brain Injuries / Q000378:metabolism; D005576:Colforsin / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D006408:Hematoma, Subdural / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D006439:Hemodynamics / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D010703:Phorbol Esters / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D011955:Receptors, Drug / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000378:metabolism; D015290:Second Messenger Systems / Q000502:physiology*
D010703:Phorbol Esters; D011943:Receptors, Adrenergic, beta; D011955:Receptors, Drug; D011976:Receptors, Muscarinic; D005576:Colforsin; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases