Journal of Applied Physiology, Vol 65, Issue 3 1099-1109, Copyright © 1988 by American Physiological Society
Central respiratory effects of glutamine synthesis inhibition in dogs
B. Hoop, D. M. Systrom, V. E. Shih and H. Kazemi
Medical Service (Pulmonary Unit), Massachusetts General Hospital, Boston.
Glutamic acid is an excitatory neurotransmitter that may have a significant
role in the central chemical drive of ventilation. Therefore
cardiorespiratory function was measured in pentobarbital
sodium-anesthetized dogs before and after central inhibition of glutamate
metabolism by means of methionine sulfoximine (MSO), a specific inhibitor
of glutamine synthase (GS) catalyzing amidation of glutamate to glutamine.
GS was inhibited centrally by perfusing the ventriculocisternal space with
artificial cerebrospinal fluid (CSF) containing 92.5 mmol MSO per liter at
a fixed pH, perfusion rate, and pressure. After GS inhibition, CSF transfer
rate of [13N]glutamine synthesized from 13NH4+ amidation of glutamate was
reduced five-fold, and minute ventilation increased from 2.90 +/- 0.41 (SE)
l/min (0.164 +/- 0.020 l.min-1.kg body wt-1) to 4.46 +/- 0.52 l/min (0.254
+/- 0.029 l.min-1.kg body wt-1). This increase in ventilation with
endogenous glutamate and the increase in ventilation previously observed
during ventriculocisternal perfusion of exogenous glutamate are compared
quantitatively via a model of central neurotransmitter glutamate
chemoreception. The results support the hypothesis that the endogenous
brain glutamate is important in the central chemical drive of ventilation.
