HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 289/1/R198    most recent 00185.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science 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 Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Mueller, P. J. Articles by Hasser, E. M. Search for Related Content PubMed PubMed Citation Articles by Mueller, P. J. Articles by Hasser, E. M.

NEUROHUMORAL CONTROL OF CARDIOVASCULAR FUNCTION

Cardiovascular response to a group III mGluR agonist in NTS requires NMDA receptors

Department of Biomedical Sciences and Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri

Submitted 19 March 2004 ; accepted in final form 16 March 2005

Previous studies have demonstrated that microinjection of the putative group III metabotropic glutamate receptor (mGluR) agonist, L(+)-2-amino-4-phosphonobutyric acid (L-AP4), into the nucleus tractus solitarius (NTS) produces depressor and sympathoinhibitory responses. These responses are significantly attenuated by a group III mGluR antagonist and may involve ionotropic glutamatergic transmission. Alternatively, a previous report in vitro suggests that preparations of L-AP4 may nonspecifically activate NMDA channels due to glycine contamination (Contractor A, Gereau RW, Green T, and Heinemann SF. Proc Natl Acad Sci USA 95: 8969–8974, 1998). Therefore, the present study tested whether responses to L-AP4 specifically require the N-methyl-D-aspartate (NMDA) receptor and whether they are due to actions at the glycine site on the NMDA channel. To test these possibilities in vivo, we performed unilateral microinjections of L-AP4, glycine, and selective antagonists into the NTS of urethane-anesthetized rats. L-AP4 (10 mM, 30 nl) produced sympathoinhibitory responses that were abolished by the NMDA receptor antagonist 2-amino-5-phosphonovaleric acid (AP-5, 10 mM) but were unaffected by the non-NMDA antagonist 6-nitro-7-sulfamobenzoquinoxaline-2,3-dione (NBQX, 2 mM). Microinjection of glycine (0.02–20 mM) failed to mimic sympathoinhibitory responses to L-AP4, even in the presence of the inhibitory glycine antagonist, strychnine (3 mM). Strychnine blocked pressor and sympathoexcitatory actions of glycine (20 mM) but failed to reveal a sympathoinhibitory component due to presumed activation of NMDA receptors. The results of these experiments suggest that responses to L-AP4 require NMDA receptors and are independent of non-NMDA receptors. Furthermore, although it is possible that glycine contamination or other nonspecific actions are responsible for the sympathoinhibitory actions of L-AP4, our data and data in the literature argue against this possibility. Thus we conclude that responses to L-AP4 in the NTS are mediated by an interaction between group III mGluRs and NMDA receptors. Finally, we also caution that nonselective actions of L-AP4 should be considered in future studies.

L-2-amino-4-phosphonobutyric acid; microinjection; metabotropic glutamate receptors; sympathetic nerve activity; nucleus tractus solitarius; N-methyl-O-aspartate

This article has been cited by other articles:

				P. J. Mueller Exercise training attenuates increases in lumbar sympathetic nerve activity produced by stimulation of the rostral ventrolateral medulla J Appl Physiol, February 1, 2007; 102(2): 803 - 813. [Abstract] [Full Text] [PDF]

				K. N. Browning, Z. Zheng, T. W. Gettys, and R. A. Travagli Vagal afferent control of opioidergic effects in rat brainstem circuits J. Physiol., September 15, 2006; 575(3): 761 - 776. [Abstract] [Full Text] [PDF]