Journal article
Novel action of nitric oxide as mediator of N-methyl-D-aspartate-induced phosphatidylinositol hydrolysis in neonatal rat cerebellum
Molecular pharmacology, v 43(1), pp 1-5
Jan 1993
PMID: 8380882
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Nitric oxide (NO) is an intercellular mediator produced within the cerebellum and other central nervous system sites. Results from the present study suggest a novel role for this gaseous second messenger in mediating the stimulatory actions of the excitatory amino acid agonist N-methyl-D-aspartate (NMDA) on turnover of phosphatidylinositol (PI) in the neonatal cerebellum. Activation of the NMDA receptor stimulates PI turnover in developing cerebellum when these neurons are in a depolarized state, but the mechanism underlying this effect is unknown. We measured changes in PI hydrolysis induced by NMDA in the presence of baclofen, which is known to depolarize neurons by activating presynaptic inhibitory gamma-aminobutyric acidB autoreceptors. NMDA increased PI hydrolysis by 80% in the presence of 1 microM baclofen. This modulatory action of NMDA was prevented by two competitive inhibitors of NO synthase, L-NG-monomethylarginine and L-N omega-nitroarginine, as well as by hemoglobin, which binds NO. Inhibition of NMDA-induced PI hydrolysis by L-NG-monomethylarginine was reversed by prior administration of L-arginine (200 microM), the physiological substrate of NO synthase. Arginine (500 microM) alone was also able to increase PI hydrolysis significantly. Superoxide dismutase, which prolongs the half-life of NO, also significantly increased the ability of NMDA to stimulate PI hydrolysis. However, NO-induced activation of the cGMP pathway did not appear to be responsible for the NMDA-induced increase in PI hydrolysis, because addition of 8-bromo-cGMP decreased this parameter, and methylene blue, which blocks guanylate cyclase activity, did not inhibit the PI hydrolysis evoked by NMDA receptor activation. These results suggest that NMDA receptor activation acts to release NO, which then acts through a novel pathway to enhance the hydrolysis of PI in the developing rat cerebellum. This novel role for NO in mediating the stimulatory actions of NMDA on PI hydrolysis may be important for developmental processes in the central nervous system.
Metrics
6 Record Views
Details
- Title
- Novel action of nitric oxide as mediator of N-methyl-D-aspartate-induced phosphatidylinositol hydrolysis in neonatal rat cerebellum
- Creators
- S S Smith - Department of Anatomy, Hahnemann University, Philadelphia, Pennsylvania 19102-1192J Li
- Publication Details
- Molecular pharmacology, v 43(1), pp 1-5
- Grant note
- NS25809 / NINDS NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- [Retired Faculty]
- Web of Science ID
- WOS:A1993KH56500001
- Scopus ID
- 2-s2.0-0027390232
- Other Identifier
- 991019184183004721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Pharmacology & Pharmacy