Alterations in cyclic AMP generation and G protein subunits following transient ischemia in gerbil hippocampus

Kazuhiko Suyama, Kuniaki Saito, Guang Chen, Bai Shen Pan, Husseini K. Manji, William Z. Potter

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

We examined alterations in the cyclic AMP generating system and G protein subunits in gerbil hippocampus following 10 min of transient ischemia. In hippocampal slices, basal and isoproterenol- and forskolin-stimulated cyclic AMP accumulations were markedly increased at 6 and 24 h after ischemia. Interestingly, both the inhibition of forskolin-stimulated cyclic AMP and the potentiation of β-adrenoceptor-stimulated cyclic AMP by a γ-aminobutyric acid(B) receptor agonist were attenuated at these time points. Ischemia did not affect the immunolabeling of any of the G protein α subunits; only that of β subunits was significantly decreased, by 28.2%, 4 days after ischemia. In contrast, pertussis toxin-catalyzed [32P]ADP ribosylation declined progressively during the late recirculation period, reaching a significant reduction (25.4%) at 6 h after ischemia. These results suggest that ischemia affects the heterotrimeric conformation (αβγ) of G(i)/G(o) during the recirculation period, thereby leading to increased cyclic AMP production. Because cyclic AMP-dependent protein kinase A modulates the α-amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid-kainate receptor channels, postischemic sensitization of the cyclic AMP generating system may contribute to neuronal degeneration in the hippocampus.

Original languageEnglish
Pages (from-to)877-885
Number of pages9
JournalJournal of Cerebral Blood Flow and Metabolism
Volume15
Issue number5
DOIs
Publication statusPublished - 1995

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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