An excitatory amino acid(s) in the ventrolateral medulla is (are) required for breathing to occur in the anesthetized cat.
The purpose of the present study was to identify sites(s) in the ventrolateral medulla where excitatory amino acids are involved in respiratory control. For this purpose, the respiratory effects produced by bilateral microinjection of excitatory amino acid antagonist drugs were examined while tidal volume (Vt), respiratory rate (f), arterial blood pressure and heart rate were monitored in chloralose-anesthetized cats. Microinjection of kynurenic acid (12.5 nmol) into a site approximately 3 mm rostral to obex, 4 mm lateral to midline and 1.5 mm below the ventral surface produced a decrease in Vt (-20 +/- 2 ml), an increase in f (+20 +/- 3 breaths/min) and a decrease in respiratory minute volume (-108 +/- 19 ml/min) (n = 8). These changes progressed to apnea in each animal tested. No significant changes in blood pressure or heart rate were observed. To determine the excitatory amino acid receptor subtype(s) involved, antagonists of n-methyl-D-aspartate (NMDA) (3-[(RS)-carboxypiperazin-4-yl]-propyl-1-phosphoric acid (CPP] and non-NMDA [6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)] receptors were microinjected bilaterally into this site. In the case of CPP, three doses were studied (0.25 nmol, n = 4; 0.75 nmol, n = 3; 2.25 nmol, n = 2). All three doses produced similar decreases in Vt (-12 +/- 1, P less than .05; -10 +/- 1, P less than .05; and -16 +/- 5 ml, respectively) and increases in f (+14 +/- 2, P less than .05; +10 +/- 3, P less than .05; and +12 +/- 3 breaths/min, respectively). None of these animals exhibited apnea.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology, Georgetown University School of Medicine, Washington, D.C.
T P
TP
Abrahams
P J
PJ
Hornby
D P
DP
Walton
A M
AM
Taveira DaSilva
R A
RA
Gillis
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000596:Amino Acids / Q000037:antagonists & inhibitors / Q000502:physiology*; D000818:Animals; D002415:Cats; D005260:Female; D005998:Glycine / Q000502:physiology; D007736:Kynurenic Acid / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology*; D008845:Microinjections; D010879:Piperazines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012119:Respiration / Q000187:drug effects / Q000502:physiology*
D000596:Amino Acids; D010879:Piperazines; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D007736:Kynurenic Acid; D005998:Glycine