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Respiratory effects produced by microinjection of L-glutamate and an uptake inhibitor of L-glutamate into the caudal subretrofacial area of the medulla.
Eur J Pharmacol. 1995 Jul 14; 280(3):257-75.EJ

Abstract

The purposes of our study were to determine the type of respiratory changes that would occur when either an excitatory amino acid receptor agonist or an uptake inhibitor was administered into the caudal subretrofacial area. This was done by microinjecting either L-glutamate or L-pyrrolidine-2,4-dicarboxylate (L-trans-2,4-PDC) into the caudal subretrofacial area while monitoring tidal volume, respiratory rate, mean arterial blood pressure and heart rate. Bilateral microinjection of 2.5 nmol of L-glutamate into the caudal subretrofacial area produced apnea in eight of eight animals tested, and the duration of apnea was 27 +/- 2 s. To determine the type of L-glutamate receptor responsible for mediating the apneic response, antagonists of the N-methyl-D-aspartate (NMDA) and non-NMDA receptor, namely, 3-[(RS)-carboxypiperazin-4-yl]-propyl-phosphonic acid (CPP), and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), respectively, were tested. Neither antagonist in doses that blocked NMDA (in the case of CPP) and amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) (in the case of CNQX) blocked apnea elicited by L-glutamate. In addition, kynurenic acid, an antagonist of NMDA and non-NMDA ionotropic receptors, failed to block the effect of L-glutamate. Microinjection of the metabotropic receptor agonist drug, trans-L-1-amino-1,3-cyclopentone-dicarboxylic acid (L-trans-ACPD), into the caudal subretrofacial area failed to have any effect on respiratory activity. Because of the inability to block the effect of L-glutamate in the caudal subretrofacial area, and the lack of effect of L-trans-ACPD, the data suggest that the apneic response produced by L-glutamate is mediated by an as yet undefined receptor. Microinjection of the L-glutamate uptake inhibitor, L-trans-2,4-PDC, was found to produce apnea. Using the dose of 0.5 nmol of L-trans-2,4-PDC, we examined the type of excitatory amino acid receptor that mediated the response. Neither pretreatment with the NMDA receptor antagonist, CPP, nor the non-NMDA receptor antagonist, CNQX, affected L-trans-2,4-PDC-induced apnea. However, combined use of these two antagonists prevented L-trans-2,4-PDC-induced apnea. These data suggest that the effect of synaptically released exitatory amino acid at the caudal subretrofacial area on breathing is apnea, and that this effect is mediated by simultaneous activation of both NMDA and non-NMDA ionotropic receptors.

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Authors+Show Affiliations

McManigle JE
Department of Pharmacology, Georgetown University School of Medicine, Washington, DC 20007, USA.
Panico WH
No affiliation info available
DaSilva AM
No affiliation info available
Gillis RA
No affiliation info available

MeSH

6-Cyano-7-nitroquinoxaline-2,3-dioneAnimalsApneaBlood PressureCatsCycloleucineDicarboxylic AcidsExcitatory Amino Acid AntagonistsFemaleGlutamic AcidHeart RateKynurenic AcidMaleNeurotoxinsNeurotransmitter Uptake InhibitorsPiperazinesPyrrolidinesReceptors, GlutamateReceptors, N-Methyl-D-AspartateRespirationRespiratory Function TestsTidal VolumeTrigeminal Caudal Nucleus

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8566094

Citation

McManigle, J E., et al. "Respiratory Effects Produced By Microinjection of L-glutamate and an Uptake Inhibitor of L-glutamate Into the Caudal Subretrofacial Area of the Medulla." European Journal of Pharmacology, vol. 280, no. 3, 1995, pp. 257-75.
McManigle JE, Panico WH, DaSilva AM, et al. Respiratory effects produced by microinjection of L-glutamate and an uptake inhibitor of L-glutamate into the caudal subretrofacial area of the medulla. Eur J Pharmacol. 1995;280(3):257-75.
McManigle, J. E., Panico, W. H., DaSilva, A. M., & Gillis, R. A. (1995). Respiratory effects produced by microinjection of L-glutamate and an uptake inhibitor of L-glutamate into the caudal subretrofacial area of the medulla. European Journal of Pharmacology, 280(3), 257-75.
McManigle JE, et al. Respiratory Effects Produced By Microinjection of L-glutamate and an Uptake Inhibitor of L-glutamate Into the Caudal Subretrofacial Area of the Medulla. Eur J Pharmacol. 1995 Jul 14;280(3):257-75. PubMed PMID: 8566094.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Respiratory effects produced by microinjection of L-glutamate and an uptake inhibitor of L-glutamate into the caudal subretrofacial area of the medulla. AU - McManigle,J E, AU - Panico,W H, AU - DaSilva,A M, AU - Gillis,R A, PY - 1995/7/14/pubmed PY - 1995/7/14/medline PY - 1995/7/14/entrez SP - 257 EP - 75 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 280 IS - 3 N2 - The purposes of our study were to determine the type of respiratory changes that would occur when either an excitatory amino acid receptor agonist or an uptake inhibitor was administered into the caudal subretrofacial area. This was done by microinjecting either L-glutamate or L-pyrrolidine-2,4-dicarboxylate (L-trans-2,4-PDC) into the caudal subretrofacial area while monitoring tidal volume, respiratory rate, mean arterial blood pressure and heart rate. Bilateral microinjection of 2.5 nmol of L-glutamate into the caudal subretrofacial area produced apnea in eight of eight animals tested, and the duration of apnea was 27 +/- 2 s. To determine the type of L-glutamate receptor responsible for mediating the apneic response, antagonists of the N-methyl-D-aspartate (NMDA) and non-NMDA receptor, namely, 3-[(RS)-carboxypiperazin-4-yl]-propyl-phosphonic acid (CPP), and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), respectively, were tested. Neither antagonist in doses that blocked NMDA (in the case of CPP) and amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) (in the case of CNQX) blocked apnea elicited by L-glutamate. In addition, kynurenic acid, an antagonist of NMDA and non-NMDA ionotropic receptors, failed to block the effect of L-glutamate. Microinjection of the metabotropic receptor agonist drug, trans-L-1-amino-1,3-cyclopentone-dicarboxylic acid (L-trans-ACPD), into the caudal subretrofacial area failed to have any effect on respiratory activity. Because of the inability to block the effect of L-glutamate in the caudal subretrofacial area, and the lack of effect of L-trans-ACPD, the data suggest that the apneic response produced by L-glutamate is mediated by an as yet undefined receptor. Microinjection of the L-glutamate uptake inhibitor, L-trans-2,4-PDC, was found to produce apnea. Using the dose of 0.5 nmol of L-trans-2,4-PDC, we examined the type of excitatory amino acid receptor that mediated the response. Neither pretreatment with the NMDA receptor antagonist, CPP, nor the non-NMDA receptor antagonist, CNQX, affected L-trans-2,4-PDC-induced apnea. However, combined use of these two antagonists prevented L-trans-2,4-PDC-induced apnea. These data suggest that the effect of synaptically released exitatory amino acid at the caudal subretrofacial area on breathing is apnea, and that this effect is mediated by simultaneous activation of both NMDA and non-NMDA ionotropic receptors. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/8566094/Respiratory_effects_produced_by_microinjection_of_L_glutamate_and_an_uptake_inhibitor_of_L_glutamate_into_the_caudal_subretrofacial_area_of_the_medulla_ L2 - https://linkinghub.elsevier.com/retrieve/pii/001429999500203W DB - PRIME DP - Unbound Medicine ER -
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