title: Alterations in cyclic AMP generation and G protein subunits following transient ischemia in gerbil hippocampus.
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 beta-adrenoceptor-stimulated cyclic AMP by a gamma-aminobutyric acidB receptor agonist were attenuated at these time points. Ischemia did not affect the immunolabeling of any of the G protein alpha subunits; only that of beta 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 (alpha beta gamma) of Gi/Go during the recirculation period, thereby leading to increased cyclic AMP production. Because cyclic AMP-dependent protein kinase A modulates the alpha-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.
authors.affiliation: Section on Clinical Pharmacology, National Institute of Mental Health, Bethesda, Maryland, USA.
authors.forename: K
authors.initials: K
authors.lastname: Suyama
authors.forename: K
authors.initials: K
authors.lastname: Saito
authors.forename: G
authors.initials: G
authors.lastname: Chen
authors.forename: B S
authors.initials: BS
authors.lastname: Pan
authors.forename: H K
authors.initials: HK
authors.lastname: Manji
authors.forename: W Z
authors.initials: WZ
authors.lastname: Potter
mesh_terms: D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002384:Catalysis; D000242:Cyclic AMP / Q000096:biosynthesis*; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005849:Gerbillinae; D006624:Hippocampus / Q000378:metabolism*; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D037342:Pertussis Toxin; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D010566:Virulence Factors, Bordetella; D000246:Adenosine Diphosphate Ribose; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins