Depressor responses to L-proline microinjected into the rat ventrolateral medulla are mediated by ionotropic excitatory amino acid receptors.
The essential amino acid L-proline produces a depressor response when microinjected into the caudal ventrolateral medulla (CVLM) of anesthetized rats. L-proline may activate some excitatory amino acid (EAA) receptors. The present study tested this hypothesis by investigating the effects of two ionotropic excitatory amino acid receptor antagonists on the depressor response to L-proline in the CVLM: the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/kainate receptor-selective antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and the N-methyl-D-aspartate (NMDA) receptor-selective antagonist MK801. Urethane-anesthetized rats received arterial catheters and their ventrolateral medulla surface was exposed. Injections of the antagonists CNQX and MK801 (2 mM, 68 nl in each case) into the CVLM completely blocked depressor responses to subsequent administration of AMPA (2 pmol/34 nl) and NMDA (2 pmol/34 nl), respectively. The depressor response to L-proline (3.4 nmol/34 nl) was strongly inhibited by prior injection of CNQX (2 mM, 68 nl) and significantly attenuated by prior injection of a high dose (20 mM, 68 nl), but not a low dose (2 mM, 68 nl), of MK801. The results indicate that the depressor response to L-proline in the CVLM includes mechanisms of ionotropic excitatory amino acid receptors.
Takemoto
Yumi
Y
Department of Neurophysiology, Division of Integrated Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Japan. yumitake@hiroshima-u.ac.jp
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects* / Q000502:physiology*; D008845:Microinjections; D016202:N-Methylaspartate / Q000494:pharmacology; D011392:Proline / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000502:physiology; D017470:Receptors, Glutamate / Q000502:physiology*; D018092:Kainic Acid Receptors / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D016291:Dizocilpine Maleate; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D016202:N-Methylaspartate; D011392:Proline; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid