QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.103.061069v1 309/2/462    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Crespi, F. Articles by Rossetti, Z. L. Search for Related Content PubMed PubMed Citation Articles by Crespi, F. Articles by Rossetti, Z. L.

NEUROPHARMACOLOGY

Pulse of Nitric Oxide Release in Response to Activation of N-Methyl-D-aspartate Receptors in the Rat Striatum: Rapid Desensitization, Inhibition by Receptor Antagonists, and Potentiation by Glycine

CEDD Psychiatry, Department of Biology, GlaxoSmithKline, Verona, Italy (F.C.); and Department of Neuroscience and CNR Institute of Neuroscience, University of Cagliari, Italy (Z.L.R.)

Increased activity of glutamate N-methyl-D-aspartate (NMDA) receptors is the dominant mechanism by which nitric oxide (NO·) is generated. By using a selective direct-current amperometry method, we characterized real time NO· release in vivo in response to chemical stimulation of NMDA receptors in the rat striatum. The application of NMDA caused the appearance of a sharp and transient oxidation signal. Concentration-response studies (10–500 µM) indicated an EC₅₀ of 48 µM. The NMDA-induced amperometric signal was suppressed by focal application of the nitric-oxide synthase inhibitor L-nitro-arginine methyl ester (L-NAME, 100 µM) or D-(-)-2-amino-5-phosphonopentanoic acid (AP-5, 100 µM) or by systemic injection of dizocilpine (1 mg/kg i.p.), drugs that, when given alone, had no effect on baseline oxidation current. Repeated injections of NMDA at short intervals (80 s) resulted in a progressive reduction of the amperometric signal with a decay half-life of 1.36 min. Sixty min after the last NMDA application the amperometric response was restored to initial levels. Finally, the coapplication of glycine (50 or 100 µM), which, when given alone had no effect, potentiated the NMDA-induced response. Thus, NMDA receptor-mediated activation of striatal NO· system shuts off quickly and undergoes rapid desensitization, suggesting a feedback inhibition of NMDA receptor function. To the extent of NO· release can represent a correlate of NMDA receptor activity, its amperometric detection could be useful to assess in vivo the state of excitatory transmission under physiological, pharmacological, or pathological conditions.

Address correspondence to: Dr. Zvani L. Rossetti, Department of Neuroscience, University of Cagliari, Cittadella di Monserrato, 09042 Monserrato (Cagliari), Italy. E-mail: rossetti{at}unica.it

This article has been cited by other articles:

				M. L. Lehmann, H. McKellar, and M. S. Erskine Coding for the Initiation of Pseudopregnancy by Temporally Patterned Activation of Amygdalar NMDA Receptors J. Neurosci., September 21, 2005; 25(38): 8696 - 8703. [Abstract] [Full Text] [PDF]

				A. Nishi, Y. Watanabe, H. Higashi, M. Tanaka, A. C. Nairn, and P. Greengard Glutamate regulation of DARPP-32 phosphorylation in neostriatal neurons involves activation of multiple signaling cascades PNAS, January 25, 2005; 102(4): 1199 - 1204. [Abstract] [Full Text] [PDF]