A novel cognition enhancer NS-105 modulates adenylate cyclase activity through metabotropic glutamate receptors in primary neuronal culture
| Autor: | Yoshinori Itoh, Fu Hai Ma, Yojiro Ukai, Shigeru Tatsumi, Yoshiaki Yoshikuni, Kiyoshi Kimura, Michiko Oka |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
medicine.medical_specialty
Proline Biology Receptors Metabotropic Glutamate Mice Cognition Piperidines Internal medicine Cyclic AMP medicine Animals Cycloleucine Virulence Factors Bordetella Cells Cultured Cerebral Cortex Neurons Pharmacology Metabotropic glutamate receptor 5 Metabotropic glutamate receptor 4 Colforsin Metabotropic glutamate receptor 7 Metabotropic glutamate receptor 6 General Medicine Cell biology Endocrinology Pertussis Toxin Metabotropic glutamate receptor Adenylate Cyclase Toxin Metabotropic glutamate receptor 1 Metabotropic glutamate receptor 2 Cyclase activity Adenylyl Cyclases |
| Zdroj: | Naunyn-Schmiedeberg's Archives of Pharmacology. 356:189-196 |
| ISSN: | 0028-1298 |
| DOI: | 10.1007/pl00005040 |
| Popis: | The effect of (+)-5-oxo-D-prolinepiperidinamide monohydrate (NS-105), a novel cognition enhancer, on adenylate cyclase activity was investigated in cultured neurons of the mouse cerebral cortex. NS-105 (10(-7) and 10(-6) M) inhibited forskolin-stimulated cyclic AMP formation, an action that was dependent on pertussis toxin-sensitive G proteins. Conversely, in pertussis toxin-pretreated neurons, NS-105 (10(-7)-10(-5) M) significantly enhanced the forskolin-stimulated cyclic AMP formation, and this action was completely reversed by cholera toxin. A metabotropic glutamate receptor agonist (1S, 3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S, 3R-ACPD) produced similar bi-directional actions on the cyclic AMP formation. Both of these inhibitory and facilitatory actions of NS-105 and 1S, 3R-ACPD were blocked by L(+)-2-amino-3-phosphopropinoic acid (L-AP3). NS-105 (10(-6) M) and 1S, 3R-ACPD (10(-4) M) significantly enhanced isoproterenol- and adenosine-stimulated cyclic AMP formation. The enhancement of such Gs-coupled receptor agonists-stimulated cyclic AMP formation was also produced by quisqualate but not by L(+)-2-amino-4-phosphonobutanoate (L-AP4). The phosphoinositides hydrolysis was enhanced by 1S, 3R-ACPD (10(-4) M) but not by NS-105 (10(-6) M), however, 1S, 3R-ACPD-induced increase in phosphoinositides turnover was attenuated by NS-105. These findings suggest that NS-105 stimulates metabotropic glutamate receptor subclasses that are coupled both negatively and positively to adenylate cyclase, but it acts as an antagonist at the receptor subclasses that are linked to phosphoinositides hydrolysis. |
| Databáze: | OpenAIRE |
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