Gossypol: a potent inhibitor of PAF‐acether‐ and leukotriene‐induced contractions of guinea‐pig lung parenchyma strips

  title={Gossypol: a potent inhibitor of PAF‐acether‐ and leukotriene‐induced contractions of guinea‐pig lung parenchyma strips},
  author={Caroline Touvay and B. Vilain and Pierre Sirois and M Soufir and Pierre G. Braquet},
  journal={Journal of Pharmacy and Pharmacology},
Gossypol, a substance extracted from cotton plants, markedly inhibited the contractile responses of guinea‐pig lung parenchyma strips stimulated with leukotriene B4 (LTB4), leukotriene D4 (LTD4) and PAF‐acether but not the responses to histamine (except at high concentration). It was slightly less potent than nordihydroguaiaretic acid (NDGA) and a PAF‐antagonist (BN 52021). From previously reported effects of gossypol on the cyclooxygenase and lipoxygenases, and on the similarity of the… Expand
Chapter 19. Modulation of Arachidonic Acid Metabolism in the Treatment of Rheumatoid Arthritis
Publisher Summary This chapter describes the nonsteroidal anti-inflammatory drugs (NSAID) literature from late 1985 to the present and discusses the treatment of inflammatory diseases from theExpand
Pharmacological Modulation of Platelet Activating Factor (PAF)‐induced Bronchoconstriction and Hypertension in Anaesthetized Guinea‐pigs
Results indicate that in anaesthetized guinea‐pigs PAF‐induced bronchoconstriction is composed of a dual response, a direct action (peak response) and an indirect action (prolonged response) that may be produced by the generation of TXA2 and lipoxygenase products, while PAF-induced hypertension is indirectly mediated by thegeneration of TX a2. Expand
Platelet-activating factor (PAF)-antagonists of natural origin.
This review is an attempt to summarize the data on PAF and action of natural PAF antagonists on it, which were evaluated by in vivo and in vitro assays. Expand
LDH-C4: a target with therapeutic potential for cancer and contraception
  • G. Gupta
  • Biology, Medicine
  • Molecular and Cellular Biochemistry
  • 2012
The salient features of LDH-C subunit and the immune responses of LDh-C4 in homologous and heterologous species are reviewed in relation to its role in acceptance or rejection of the allograft and its application in contraception and immunotherapy of cancer, directly or indirectly through the regulation of its substrate, the lactate. Expand
Generating and Screening a Natural Product Library for CYclooxygenase and Lipoxygenase Dual Inhibitors
ABSTRACT Natural products are a highly diversified structural pool for the discovery of potential drug leads. Recent technological developments in the fields of high throughput purification,Expand


The action of leukotriene B4 (LTB4) on the lung.
It is suggested that in the lung, LTB4 is a myotropic agent three times more powerful than histamine, that it stimulated a receptor which is different of histamine of SRS-A receptors, and that its contractile action in the lungs is mediated by prostaglandins and thromboxanes. Expand
Characterization of platelet activating factor (PAF)-acether-induced contractions of guinea-pig lung strips by selected inhibitors of arachidonic acid metabolism and by PAF-acether antagonists.
The contractile response of the lung parenchyma to PAF-acether was inhibited by aspirin, imidazole and OKY-046, which suggested that thromboxane A2 might play a mediator role inPAF-induced contractions. Expand
Further studies on the mechanism of action of leukotrienes and histamine on guinea pig lung parenchyma. Role of calcium, phospholipase and methyltransferase.
The results confirmed the important role of extracellular and intracellular calcium in the myotropic activity of leukotrienes and histamine in guinea pig lungs and showed that compounds which interfere either directly or indirectly with calcium mobilization into the lung smooth muscles, decreased the tissue responsiveness. Expand
Evidence for a mediator role of thromboxane A2 in the myotropic action of leukotriene B4 (LTB4) on the guinea-pig lung.
Since parenchymal strips do not appear to be very sensitive to PGF2 alpha, PGE2 and the endoperoxides, and since effluents from LTB4-treated lungs produced contractions of lung strip and rabbit aorta which were reduced after 5 min, thromboxane A2 was postulated to mediate the lung effect of L TB4. Expand
Gossypol, a potent inhibitor of arachidonate 5- and 12-lipoxygenases.
Gossypol inhibited 5- and 12-lipoxygenases of rat basophilic leukemia (RBL-1) cells with ID50 of 0.3 microM and 0.7 microM, respectively, and was of a non-competitive type with respect to arachidonate. Expand
Inhibition by gossypol of phospholipid-sensitive Ca2+-dependent protein kinase from pig testis.
Results suggested that a phospholipid-sensitive Ca2+-dependent protein phosphorylation system in the testis is involved in the regulation of spermatogenesis. Expand
Role of cyclooxygenase products in the lung action of leukotrienes A4, B4, C4, D4 and E4.
The role of prostaglandin F2 alpha, thromboxane B2 and 12-hydroxyheptadecatrienoic acid by guinea pig lungs following stimulation with LTB4 and LTD4 was measured and stimulation of their release by the peptidoleukotrienes is many times more effective than by L TB4. Expand
The mechanism of action of leukotrienes C4 and D4 in guinea-pig isolated perfused lung and parenchymal strips of guinea pig, rabbit and rat.
It appears that a major part of the constrictor actions of LTC4 and LTD4 in guinea-pig lung are mediated by myotropic cyclo-oxygenase products, i.e. thromboxane A2 (TxA2) and prostaglandins (PGs). Expand
Molecular mechanisms of gossypol action on lipid membranes.
The interactions of gossypol with lipid monolayer and bilayer membranes are characterized in order to assess if the drug acts by modifying the electrochemical properties of membranes and to account for the mitochondrial uncoupling effects of this molecule. Expand
Studies on the nature of the inhibition by gossypol of the transformation of pepsinogen to pepsin.
It is apparent that intra- as well as intermolecular cross-linkages may occur and the optical rotatory dispersion and circular dichroism differ from those of pepsinogen. Expand