Effects of ketamine and fentanyl on lung metabolism in perfused rat lungs

Dan C Martin, A. M. Carr, R. R. Livingston, C. A. Watkins

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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 μM) 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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume257
Issue number3
StatePublished - Jan 1 1989

Fingerprint

Ketamine
Fentanyl
Serotonin
Lung
Peptidyl-Dipeptidase A
Hydroxyindoleacetic Acid
Proteins
Phenylalanine
Pharmaceutical Preparations
Hydrolysis
Salts
Pharmacology
Acids
Membranes
Enzymes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

Cite this

Effects of ketamine and fentanyl on lung metabolism in perfused rat lungs. / Martin, Dan C; Carr, A. M.; Livingston, R. R.; Watkins, C. A.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 257, No. 3, 01.01.1989.

Research output: Contribution to journalArticle

@article{b698d506dab64910ac0b56519cdd38b6,
title = "Effects of ketamine and fentanyl on lung metabolism in perfused rat lungs",
abstract = "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 μM) 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.",
author = "Martin, {Dan C} and Carr, {A. M.} and Livingston, {R. R.} and Watkins, {C. A.}",
year = "1989",
month = "1",
day = "1",
language = "English (US)",
volume = "257",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "3",

}

TY - JOUR

T1 - Effects of ketamine and fentanyl on lung metabolism in perfused rat lungs

AU - Martin, Dan C

AU - Carr, A. M.

AU - Livingston, R. R.

AU - Watkins, C. A.

PY - 1989/1/1

Y1 - 1989/1/1

N2 - 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 μM) 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.

AB - 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 μM) 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.

UR - http://www.scopus.com/inward/record.url?scp=0024424714&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0024424714&partnerID=8YFLogxK

M3 - Article

VL - 257

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

IS - 3

ER -