title: Differential responses of rat cerebral somatostatinergic and cholinergic cells to glutamate agonists.
abstract: Reductions in cortical somatostatin (SRIH) and choline acetyl-transferase (ChAT) are major biochemical deficits in Alzheimer disease (AD). SRIH and ChAT were measured in fetal rat cerebral neurons after exposure to the glutamate agonists N-methyl-D-aspartate (NMDA), kainate (KA), and quisqualate (Q). NMDA (96 h incubation) stimulated SRIH release and content in a dose-dependent manner with a Bmax of 10(-5)M and EC50 of 2-3 x 10(-6)M. KA showed a small stimulation in SRIH levels at 10(-5)M, but produced marked inhibition at 10(-4)M. Q decreased both intracellular and secreted SRIH. KA (51-76% of basal) and Q (27-56% of basal) but not NMDA (91-114% of basal) also inhibited the incorporation of [35S]methionine into proteins. In similar experiments 10(-4)M Q (23 +/- 9% of basal) and KA (20 +/- 3% of basal) but not NMDA (80 +/- 16% of basal) reduced ChAT levels in hypothalamic/septal cultures. These inhibitory actions on ChAT activity by KA and Q were reversed by gamma-glutamyltaurine (GT) but not by 2-amino-5-phosphonopentanoic acid (AP5). Chronic NMDA exposure partially inhibited muscarinic acetylcholine receptor (mAChR) mediated inositol phospholipid (PI) turnover, whereas it was abolished after KA and Q pretreatment. These findings suggest that in cerebral cell cultures, NMDA has a stimulatory action on somatostatinergic neurons and non-NMDA receptor agonism could play an important role in EAA-mediated neural damage.
authors.affiliation: Department of Medicine, University of Wales College of Medicine, Heath Park, Cardiff, UK.
authors.forename: J
authors.initials: J
authors.lastname: Ham
authors.forename: R
authors.initials: R
authors.lastname: Duberley
authors.forename: C
authors.initials: C
authors.lastname: Rickards
authors.forename: M F
authors.initials: MF
authors.lastname: Scanlon
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D005260:Female; D005971:Glutamates / Q000502:physiology*; D018698:Glutamic Acid; D007295:Inositol Phosphates / Q000378:metabolism; D007608:Kainic Acid / Q000494:pharmacology; D007700:Kinetics; D016202:N-Methylaspartate / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009474:Neurons / Q000502:physiology; D010275:Parasympathetic Nervous System / Q000166:cytology / Q000502:physiology*; D011247:Pregnancy; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000502:physiology; D013004:Somatostatin / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*
chemical_list: D005971:Glutamates; D007295:Inositol Phosphates; D009419:Nerve Tissue Proteins; D011950:Receptors, Cholinergic; D018698:Glutamic Acid; D013004:Somatostatin; D016202:N-Methylaspartate; D016318:Quisqualic Acid; D002795:Choline O-Acetyltransferase; D007608:Kainic Acid