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

Patrick J. Mueller, C. Michael Foley, Helen W. Vogl, Meredith Hay, Eileen M. Hasser

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume289
Issue number1 58-1
DOIs
StatePublished - Jul 2005
Externally publishedYes

Fingerprint

Excitatory Amino Acid Agonists
Metabotropic Glutamate Receptors
Solitary Nucleus
N-Methyl-D-Aspartate Receptors
Glycine
Microinjections
D-Aspartic Acid
Strychnine
N-Methylaspartate
2-amino-4-phosphono-propinate
2-Amino-5-phosphonovalerate
Excitatory Amino Acid Antagonists
Urethane

Keywords

  • L-2-amino-4-phosphonobutyric acid
  • Metabotropic glutamate receptors
  • Microinjection
  • N-methyl-o-aspartate
  • Nucleus tractus solitarius
  • Sympathetic nerve activity

ASJC Scopus subject areas

  • Physiology

Cite this

Cardiovascular response to a group III mGluR agonist in NTS requires NMDA receptors. / Mueller, Patrick J.; Foley, C. Michael; Vogl, Helen W.; Hay, Meredith; Hasser, Eileen M.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 289, No. 1 58-1, 07.2005.

Research output: Contribution to journalArticle

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AU - Hasser, Eileen M.

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