The effect of inhibitors on the LTD4-induced contractions and release of thromboxane A2 in the guinea pig lung parenchymal strip.
Identifieur interne : 003548 ( Main/Exploration ); précédent : 003547; suivant : 003549The effect of inhibitors on the LTD4-induced contractions and release of thromboxane A2 in the guinea pig lung parenchymal strip.
Auteurs : J E Vincent ; F J Zijlstra ; I L BontaSource :
- Agents and actions. Supplements [ 0379-0363 ] ; 1984.
Descripteurs français
- KwdFr :
- Animaux, Chloroquine (pharmacologie), Cochons d'Inde, Dosage radioimmunologique, Femelle, Indométacine (pharmacologie), Mâle, Poumon (), Poumon (métabolisme), Relation dose-effet des médicaments, Substances à réaction différée de l'anaphylaxie (antagonistes et inhibiteurs), Substances à réaction différée de l'anaphylaxie (pharmacologie), Thromboxane A2 (métabolisme), Xanthine(isobutyl-3 methyl-1) (pharmacologie).
- MESH :
- antagonistes et inhibiteurs : Substances à réaction différée de l'anaphylaxie.
- métabolisme : Poumon, Thromboxane A2.
- pharmacologie : Chloroquine, Indométacine, Substances à réaction différée de l'anaphylaxie, Xanthine(isobutyl-3 methyl-1).
- Animaux, Cochons d'Inde, Dosage radioimmunologique, Femelle, Mâle, Poumon, Relation dose-effet des médicaments.
English descriptors
- KwdEn :
- 1-Methyl-3-isobutylxanthine (pharmacology), Animals, Chloroquine (pharmacology), Dose-Response Relationship, Drug, Female, Guinea Pigs, Indomethacin (pharmacology), Lung (drug effects), Lung (metabolism), Male, Radioimmunoassay, SRS-A (antagonists & inhibitors), SRS-A (pharmacology), Thromboxane A2 (metabolism).
- MESH :
- chemical , antagonists & inhibitors : SRS-A.
- chemical , metabolism : Thromboxane A2.
- chemical , pharmacology : 1-Methyl-3-isobutylxanthine, Chloroquine, Indomethacin, SRS-A.
- drug effects : Lung.
- metabolism : Lung.
- Animals, Dose-Response Relationship, Drug, Female, Guinea Pigs, Male, Radioimmunoassay.
Abstract
The guinea-pig lung parenchymal (GPLP) strip is sensitive to leukotrienes (LT) C4 and D4 (LTC4 and LTD4). These substances induce contractions during which thromboxane (TX) A2 (TxA2) is released. This event was measured both by bioassay of TxA2 and radioimmunoassay of thromboxane B2 (TxB2). Indomethacin partially inhibited the contractile response and completely abolished the release of TxA2. The proportional participation of TxA2 in the contractile response was calculated quantitatively, and appeared to be 70-90%. On basis of these results, it is concluded that only a small proportion of the contractions is due to the direct action of the leukotrienes and a major part to the formed thromboxane A2. The action of the phospholipase A2 (PLA2) inhibitor chloroquine and the phosphodiesterase inhibitor, 3-isobutyl-1-methyl-xanthine (IBMX), were measured both on the contraction and the TxA2 release. Chloroquine in a dose of 40 /micrograms/ml totally inhibited the TxA2 release induced by 50 ng LTD4. At higher doses, the contractions were also completely inhibited. IBMX in a dose of 22 /micrograms/ml inhibited both the contraction and the TxA2 release to a large extent. These effects are most probably due to an inhibition of the phospholipase A2 which is activated by the leukotrienes. It is supposed that chloroquine acts directly and that the action of IBMX is due to an increase in cyclic AMP, which also leads to an inhibition of the enzyme. After the incubation of lung strips with [1-14C] arachidonic acid (AA), mainly TxB2 and lipoxygenase products are formed.
PubMed: 6206700
Affiliations:
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Le document en format XML
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Supplements</title><idno type="ISSN">0379-0363</idno><imprint><date when="1984" type="published">1984</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>1-Methyl-3-isobutylxanthine (pharmacology)</term><term>Animals</term><term>Chloroquine (pharmacology)</term><term>Dose-Response Relationship, Drug</term><term>Female</term><term>Guinea Pigs</term><term>Indomethacin (pharmacology)</term><term>Lung (drug effects)</term><term>Lung (metabolism)</term><term>Male</term><term>Radioimmunoassay</term><term>SRS-A (antagonists & inhibitors)</term><term>SRS-A (pharmacology)</term><term>Thromboxane A2 (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Chloroquine (pharmacologie)</term><term>Cochons d'Inde</term><term>Dosage radioimmunologique</term><term>Femelle</term><term>Indométacine (pharmacologie)</term><term>Mâle</term><term>Poumon ()</term><term>Poumon (métabolisme)</term><term>Relation dose-effet des médicaments</term><term>Substances à réaction différée de l'anaphylaxie (antagonistes et inhibiteurs)</term><term>Substances à réaction différée de l'anaphylaxie (pharmacologie)</term><term>Thromboxane A2 (métabolisme)</term><term>Xanthine(isobutyl-3 methyl-1) (pharmacologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>SRS-A</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Thromboxane A2</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>1-Methyl-3-isobutylxanthine</term><term>Chloroquine</term><term>Indomethacin</term><term>SRS-A</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Substances à réaction différée de l'anaphylaxie</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Lung</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Lung</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Poumon</term><term>Thromboxane A2</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Chloroquine</term><term>Indométacine</term><term>Substances à réaction différée de l'anaphylaxie</term><term>Xanthine(isobutyl-3 methyl-1)</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Dose-Response Relationship, Drug</term><term>Female</term><term>Guinea Pigs</term><term>Male</term><term>Radioimmunoassay</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cochons d'Inde</term><term>Dosage radioimmunologique</term><term>Femelle</term><term>Mâle</term><term>Poumon</term><term>Relation dose-effet des médicaments</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The guinea-pig lung parenchymal (GPLP) strip is sensitive to leukotrienes (LT) C4 and D4 (LTC4 and LTD4). These substances induce contractions during which thromboxane (TX) A2 (TxA2) is released. This event was measured both by bioassay of TxA2 and radioimmunoassay of thromboxane B2 (TxB2). Indomethacin partially inhibited the contractile response and completely abolished the release of TxA2. The proportional participation of TxA2 in the contractile response was calculated quantitatively, and appeared to be 70-90%. On basis of these results, it is concluded that only a small proportion of the contractions is due to the direct action of the leukotrienes and a major part to the formed thromboxane A2. The action of the phospholipase A2 (PLA2) inhibitor chloroquine and the phosphodiesterase inhibitor, 3-isobutyl-1-methyl-xanthine (IBMX), were measured both on the contraction and the TxA2 release. Chloroquine in a dose of 40 /micrograms/ml totally inhibited the TxA2 release induced by 50 ng LTD4. At higher doses, the contractions were also completely inhibited. IBMX in a dose of 22 /micrograms/ml inhibited both the contraction and the TxA2 release to a large extent. These effects are most probably due to an inhibition of the phospholipase A2 which is activated by the leukotrienes. It is supposed that chloroquine acts directly and that the action of IBMX is due to an increase in cyclic AMP, which also leads to an inhibition of the enzyme. After the incubation of lung strips with [1-14C] arachidonic acid (AA), mainly TxB2 and lipoxygenase products are formed.</div></front></TEI><affiliations><list></list><tree><noCountry><name sortKey="Bonta, I L" sort="Bonta, I L" uniqKey="Bonta I" first="I L" last="Bonta">I L Bonta</name><name sortKey="Vincent, J E" sort="Vincent, J E" uniqKey="Vincent J" first="J E" last="Vincent">J E Vincent</name><name sortKey="Zijlstra, F J" sort="Zijlstra, F J" uniqKey="Zijlstra F" first="F J" last="Zijlstra">F J Zijlstra</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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