Effects of ketamine and fentanyl on lung metabolism in perfused rat lungs.
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.
Martin
D C
DC
Department of Anesthesiology, Medical College of Georgia, Augusta 30912.
Carr
A M
AM
Livingston
R R
RR
Watkins
C A
CA
D000818:Animals; D005283:Fentanyl / Q000008:administration & dosage / Q000494:pharmacology*; D007649:Ketamine / Q000008:administration & dosage / Q000494:pharmacology*; D008168:Lung / Q000378:metabolism*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D010477:Perfusion; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism / Q000493:pharmacokinetics
D011506:Proteins; D012701:Serotonin; D007649:Ketamine; D007703:Peptidyl-Dipeptidase A; D005283:Fentanyl