Effect of injury on the bi-affinity alpha 1-adrenoreceptor binding in rat brain in vivo.
Focal freezing lesions in rats cause a widespread decrease of cortical glucose utilization in the lesioned hemisphere, probably as a reflection of depressed cortical activity. The noradrenergic neurotransmitter system was implicated in these alterations when it was demonstrated that prazosin, a specific norepinephrine (NE) antagonist at alpha 1-adrenergic receptors, prevented their development. In normal rat brain, specific binding of [125I]HEAT [(+/-)2-(3-[125I]iodo-4-hydroxyphenyl)-ethyl-aminomethyl-tetralone], another selective alpha 1-adrenoreceptor ligand, was demonstrated in vivo at sites consistent with the alpha 1A- and alpha 1B-adrenoreceptor subtypes. In the present study, the effect of a freezing lesion on specific binding of [125I]HEAT in rat brain in vivo was determined three days after traumatization when cortical glucose use suggested the greatest degree of functional depression. The steady-state volumes of distribution of [125I]HEAT three days after injury were significantly increased in all the cortical areas of the lesioned hemisphere, but not in the subcortical structures. Injury did not modify the binding affinities for HEAT. However, a statistically significant increase in the number of low-affinity binding sites for this ligand was demonstrated in all cortical areas of the lesioned hemisphere, but not in subcortical structures. The traumatization did not modify Bmax estimates for the high-affinity binding of HEAT. The results support the hypothesis that changes in the noradrenergic system are of functional importance in brain injury and that at least some effects of injury are mediated by alpha 1B-adrenergic receptors.
Dyve
S
S
Positron Imaging Laboratories, McGill University, Montreal, Quebec, Canada.
Yang
Y J
YJ
McHugh
M
M
Gjedde
A
A
Pappius
H M
HM
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000473:pathology*; D001930:Brain Injuries; D002352:Carrier Proteins; D002540:Cerebral Cortex; D005615:Freezing; D007700:Kinetics; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*
D002352:Carrier Proteins; D018340:Receptors, Adrenergic, alpha-1