Cyclic-AMP mediated drugs: differential or global reduction of eicosanoid synthesis in the isolated rat lung?

In this study the question was addressed whether cAMP mediated drugs induce a differential reduction of branches of the arachidonic acid metabolism rather than a global reduction of eicosanoid synthesis. The isolated lungs of actively sensitized rats were employed to study prostaglandin and leukotriene release in the presence and absence of the cAMP mediated drugs theophylline, milrinone, sulmazole, isobutyl-methylxanthine and salbutamol. The release of eicosanoids as measured by RIA was predominantly basal and continuous, with a mild antigen induced stimulation only for TXB2and the leukotrienes. All drugs reduced eicosanoid release globally. It is concluded that cAMP mediated drugs interfere with arachidonic acid metabolism at a site proximal to the branching into lipoxygenase and cyclo-oxygenase pathways.

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Pharmacological modulation of arachidonic acid metabolism in the isolated rat lung by selective phosphodiesterase inhibitors

European Journal of Pharmacology ◽

10.1016/0014-2999(90)93646-8 ◽

1990 ◽

Vol 183 (6) ◽

pp. 2126-2127

Author(s):

M.J. Post ◽

J.D. te Biesebeek ◽

J. Wemer ◽

H.H. van Rooij ◽

A.J. Porsius

Keyword(s):

Arachidonic Acid ◽

Acid Metabolism ◽

Phosphodiesterase Inhibitors ◽

Arachidonic Acid Metabolism ◽

Rat Lung ◽

Pharmacological Modulation ◽

Isolated Rat Lung ◽

Isolated Rat

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Effects of milrinone and salbutamol on antigen induced arachidonic acid metabolism in the isolated rat lung

Biochemical Pharmacology ◽

10.1016/0006-2952(89)90539-x ◽

1989 ◽

Vol 38 (16) ◽

pp. 2573-2574 ◽

Cited By ~ 2

Author(s):

M.J. Post ◽

J.D. Te Biesebeek ◽

J. Wemer ◽

H.H. Van Rooij ◽

F.J. Zijlstra ◽

...

Keyword(s):

Arachidonic Acid ◽

Acid Metabolism ◽

Arachidonic Acid Metabolism ◽

Rat Lung ◽

Isolated Rat Lung ◽

Isolated Rat

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A study of ozone-induced edema in the isolated rat lung in relation to arachidonic acid metabolism, mixed-function oxidases and angiotensin converting enzyme activities

Pulmonary Pharmacology ◽

10.1016/0952-0600(90)90034-g ◽

1990 ◽

Vol 3 (2) ◽

pp. 65-72

Author(s):

S. Dutta ◽

M. Chatterjee ◽

T.N. Teknos ◽

R.W. Carlson

Keyword(s):

Arachidonic Acid ◽

Angiotensin Converting Enzyme ◽

Enzyme Activities ◽

Acid Metabolism ◽

Arachidonic Acid Metabolism ◽

Converting Enzyme ◽

Rat Lung ◽

Mixed Function Oxidases ◽

Isolated Rat Lung ◽

Isolated Rat

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Indomethacin inhibits arachidonic acid metabolism via lipoxygenase and cyclo-oxygenase in hamster isolated lungs

Prostaglandins and Medicine ◽

10.1016/0161-4630(81)90049-5 ◽

1981 ◽

Vol 7 (6) ◽

pp. 591-599 ◽

Cited By ~ 24

Author(s):

Pekka Uotila ◽

Jussi Männistö ◽

Niklas Simberg ◽

Kaarlo Hartiala

Keyword(s):

Arachidonic Acid ◽

Acid Metabolism ◽

Arachidonic Acid Metabolism ◽

Isolated Lungs

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Aspirin inhibits arachidonic acid metabolism via lipoxygenase and cyclo-oxygenase in hamster isolated lungs

Prostaglandins ◽

10.1016/s0090-6980(82)80011-7 ◽

1982 ◽

Vol 23 (5) ◽

pp. 731-741 ◽

Cited By ~ 19

Author(s):

Hannu Paajanen ◽

Jussi Männistö ◽

Pekka Uotila

Keyword(s):

Arachidonic Acid ◽

Acid Metabolism ◽

Arachidonic Acid Metabolism ◽

Isolated Lungs

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Distribution of cyclooxygenase products with cyclooxygenase inhibition in isolated dog lung

Journal of Applied Physiology ◽

10.1152/jappl.1986.61.3.988 ◽

1986 ◽

Vol 61 (3) ◽

pp. 988-993 ◽

Cited By ~ 8

Author(s):

M. R. Littner ◽

G. M. Kazmi ◽

F. D. Lott

Keyword(s):

Arachidonic Acid ◽

Salt Solution ◽

Marked Reduction ◽

Acid Metabolism ◽

Enzyme Inhibitor ◽

Lung Parenchyma ◽

Selective Inhibition ◽

Arachidonic Acid Metabolism ◽

Prostaglandin F2 Alpha ◽

Isolated Lungs

Arachidonic acid metabolism can lead to synthesis of cyclooxygenase products in the lung as indicated by measurement of such products in the perfusate of isolated lungs perfused with a salt solution. However, a reduction in levels of cyclooxygenase products in the perfusate may not accurately reflect the inhibition of levels of such products as measured in lung parenchyma. We infused sodium arachidonate into the pulmonary circulation of isolated dog lungs perfused with a salt solution and measured parenchymal, as well as perfusate, levels of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), prostaglandin F2 alpha (PGF2 alpha), prostaglandin E2 (PGE2), and thromboxane B2 (TxB2). These studies were repeated with indomethacin (a cyclooxygenase enzyme inhibitor) in the perfusate. We found that indomethacin leads to a marked reduction in perfusate levels of PGF2 alpha, PGE2, 6-keto-PGF1 alpha, and TxB2, as well as a marked reduction in parenchymal levels of 6-keto-PGF1 alpha and TxB2 when parenchymal levels of PGF2 alpha and PGE2 are not reduced. We conclude that, with some cyclooxygenase products, a reduction in levels of these products in the perfusate of isolated lungs may not indicate inhibition of levels of these products in the lung parenchyma and that a reduction in one parenchymal product may not predict the reduction of other parenchymal products. It can be speculated that some of the physiological actions of indomethacin in isolated lungs may result from incomplete or selective inhibition of synthesis of pulmonary cyclooxygenase products.

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