AJP - Endocrinology and Metabolism, Vol 257, Issue 3 E379-E384, Copyright © 1989 by American Physiological Society
Effects of ketamine and fentanyl on lung metabolism in perfused rat lungs
D. C. Martin, A. M. Carr, R. R. Livingston and C. A. Watkins
Department of Anesthesiology, Medical College of Georgia, Augusta 30912.
The effects of ketamine and fentanyl on serotonin (5-hydroxytryptamine;
5-HT) metabolism, angiotensin-converting enzyme (ACE), and protein
synthesis (PS) were investigated in an isolated lung model. Rat lungs were
perfused in situ with a blood-free physiological salt solution. The
pulmonary vasculature was exposed to ketamine (0.005-2.1 mM) or fentanyl
(1.8-4.5 microM) for up to 2 h. After 1 h, accumulation of
5-[14C]hydroxyindoleacetic acid (5-HIAA) by the lung was monitored as an
index of 5-HT metabolism. ACE activity was estimated from hydrolysis of
[3H]benzoylphenylalanyl-alanyl-proline, a synthetic substrate for the
enzyme. [3H]phenylalanine was added to the perfusate after 1 h, and its
incorporation into acid-precipitable lung protein was measured over the
subsequent hour. Ketamine inhibited 5-HT uptake in a concentration-related
manner. The inhibition was characterized as competitive and reversible.
Fentanyl had no effect on lung 5-HIAA accumulation. Neither drug altered
ACE activity or protein synthesis over the concentration ranges tested. The
results indicate an action by ketamine that inhibits the 5-HT
membrane-transport process. The different effects observed by ketamine and
fentanyl on this process could contribute to the diverse pharmacological
properties of these two drugs.
