Alteration of second-messenger ligand binding following 2-hr hemispheric ischemia in the gerbil brain.
The alterations of second-messenger ligand binding and cerebral blood flow (CBF) were evaluated in the gerbil brain after 2-h unilateral common carotid artery occlusion. [3H]Forskolin (FK) and [3H]phorbol-12,13-dibutyrate (PDBu) were used as specific ligands for adenylate cyclase (AC) and protein kinase C (PKC) activity estimation, respectively. CBF was determined at the end of the experiment by the [14C]iodoantipyrine method. A quantitative autoradiographic method permitted simultaneous measurement of the three parameters in the same brain. The levels in the caudate-putamen, globus pallidus, and hippocampus were analyzed. The animals were divided into three groups: Group 1 with severe ischemia (CBF in the lateral nuclei of the thalamus (CBFt) less than 50 ml/100 g/min), Group 2 with mild ischemia (CBFt greater than or equal to 50 ml/100 g/min), and the Sham Group. The PDBu binding revealed a statistically significant increase in the caudate-putamen, lateral nuclei of the thalamus and hippocampus (CA1 and CA3 regions and dentate gyrus) on the ischemic side in Group 1 as compared to that in Group 2 and the Sham Group. In contrast, the FK binding did not show any significant changes in any of the regions. These data and our previous findings for 6-h ischemia suggest that (1) PKC translocation to the cell membrane may occur at the early ischemic phase in particular regions including the caudate-putamen, lateral nuclei of the thalamus and hippocampus, with the translocated PKC gradually diminishing during the subsequent ischemic period; and (2) the suppression of the AC system observed in 6-h ischemia may not appear in the early ischemic phase.
Tanaka
K
K
Department of Neurology, School of Medicine, Keio University, Tokyo, Japan.
Fukuuchi
Y
Y
Gomi
S
S
Takashima
S
S
Mihara
B
B
Shirai
T
T
Nogawa
S
S
Nozaki
H
H
Nagata
E
E
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives; D001345:Autoradiography; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D002250:Carbon Radioisotopes; D017536:Carotid Artery, Common; D005576:Colforsin / Q000378:metabolism*; D005260:Female; D005849:Gerbillinae; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000503:physiopathology; D008024:Ligands; D008297:Male; D009928:Organ Specificity; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D012039:Regional Blood Flow; D015290:Second Messenger Systems / Q000502:physiology*; D013997:Time Factors; D014316:Tritium
D002250:Carbon Radioisotopes; D008024:Ligands; D014316:Tritium; D005576:Colforsin; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D000983:Antipyrine; C008135:iodoantipyrine