POSTISCHEMIC BINDING OF [H-3] PHORBOL 12,13-DIBUTYRATE AND [H-3] INOSITOL 1,4,5-TRISPHOSPHATE IN THE GERBIL BRAIN - AN AUTORADIOGRAPHIC STUDY

Postischemic alteration of second messenger systems was investigated in the Mongolian gerbil, utilizing [H-3]phorbol 12,13-dibutyrate and [H-3]inositol 1,4,5-trisphosphate receptor autoradiography. Transient ischemia was induced for 10 min, and animals were allowed to survive for various recirculation periods of up to one month. [H-3]Phorbol 12,13-dibutyrate binding in selectively vulnerable areas showed no significant change 1-24 h after ischemia except for a transient decline in a few regions. Thereafter, the binding in most of the selectively vulnerable areas showed significant alteration 48 h or seven days after ischemia. Interestingly, dentate molecular layer which was resistant to ischemia showed a significant elevation in the number of [H-3]phorbol 12,13-dibutyrate binding sites. One month after ischemia, [H-3]phorbol 12,13-dibutyrate binding showed significant reduction only in the striatum and the hippocampal CA1 sector where severe neuronal damage was seen morphologically. A significant elevation in the number of [H-3]phorbol 12,13-dibutyrate binding sites was still seen in the dentate molecular layer one month after ischemia. In contrast, [H-3]inositol 1,4,5-trisphosphate binding showed significant reduction in the selectively vulnerable regions 1-24 h after ischemia. Thereafter, [H-3]inositol 1,4,5-trisphosphate binding in most of the selectively vulnerable areas markedly decreased up to one month after ischemia. In the dentate molecular layer, [H-3]inositol 1,4,5-trisphosphate binding also showed significant reduction during recirculation except for a slight recovery 48 h and seven days after ischemia. One month after ischemia, the binding in all regions showed significant reduction. These results suggest that postischemic alteration of two second messenger (protein kinase C and inositol 1,4,5-trisphosphate) binding sites was produced with different processes in selectively vulnerable areas. Furthermore, they suggest that the disruption of intracellular calcium-homeostasis may play a key role in the pathogenesis of ischemic neuronal damage. These findings suggest that marked alteration of intracellular signal transduction may precede the neuronal damage to the selectively vulnerable areas.