Abstract
Nootropic agents are proposed to serve as cognition enhancers. The underlying mechanism, however, is largely unknown. The present study was conducted to assess the intracellular signal transduction pathways mediated by the nootropic nefiracetam in the native and mutantTorpedo californica nicotinic acetylcholine (ACh) receptors expressed in Xenopus laevis oocytes. Nefiracetam induced a short-term depression of ACh-evoked currents at submicromolar concentrations (0.01–0.1 μm) and a long-term enhancement of the currents at micromolar concentrations (1–10 μm). The depression was caused by activation of pertussis toxin-sensitive, G protein-regulated, cAMP-dependent protein kinase (PKA) with subsequent phosphorylation of the ACh receptors; in contrast, the enhancement was caused by activation of Ca2+-dependent protein kinase C (PKC) and the ensuing PKC phosphorylation of the receptors. Therefore, nefiracetam interacts with PKA and PKC pathways, which may explain a cellular mechanism for the action of cognition-enhancing agents.
Footnotes
- Received August 19, 1997.
- Accepted October 9, 1997.
-
Send reprint requests to: Dr. Tomoyuki Nishizaki, Department of Physiology, Kobe University School of Medicine, 7–5-1 kusunoki-cho, Chuo-ku, Kobe 650, Japan. E-mail:tomo{at}med.kobe-u.ac.jp
-
This work was supported in part by a research grant from the Muscular Dystrophy Association.
- The American Society for Pharmacology and Experimental Therapeutics
MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|
Log in using your username and password
Purchase access
In this issue
Nefiracetam Modulates Acetylcholine Receptor Currents via Two Different Signal Transduction Pathways
