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

13 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 - 01-01-1995
Externally publishedYes

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Gerbillinae
Protein Subunits
GTP-Binding Proteins
Cyclic AMP
Hippocampus
Ischemia
Colforsin
Cyclic AMP-Dependent Protein Kinases
Aminobutyrates
Kainic Acid Receptors
Pertussis Toxin
Isoproterenol
Adenosine Diphosphate
Adrenergic Receptors
Acids

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Cite this

Suyama, Kazuhiko ; Saito, Kuniaki ; Chen, Guang ; Pan, Bai Shen ; Manji, Husseini K. ; Potter, William Z. / Alterations in cyclic AMP generation and G protein subunits following transient ischemia in gerbil hippocampus. In: Journal of Cerebral Blood Flow and Metabolism. 1995 ; Vol. 15, No. 5. pp. 877-885.
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Alterations in cyclic AMP generation and G protein subunits following transient ischemia in gerbil hippocampus. / Suyama, Kazuhiko; Saito, Kuniaki; Chen, Guang; Pan, Bai Shen; Manji, Husseini K.; Potter, William Z.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 15, No. 5, 01.01.1995, p. 877-885.

Research output: Contribution to journalArticle

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