Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Autacoids”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 757 records · Page 42Linked to original sources
PubMed1980

Modifications of drinking behaviour and of arterial blood pressure induced by tachykinins in rats and pigeons.

Intracerebroventricular injections of the naturally occurring tachykinins eledoisin, physalaemin and substance P elicit a powerful antidipsogenic effect in the rat, while in the pigeon they potently stimulate water intake. The aim of this paper was to study in conscious rats and pigeons the vascular effect of these peptides and to compare this effect to the one elicited on water intake. The results of these experiments demonstrate that there is no direct relationship between the two effects. Our findings suggest that the effect of these peptides on water intake might be specific on CNS and not related to their vascular activity.

Animals↗
PubMed1975

Histamine release, formation of prostaglandin-like activity (SRS-C) and mast cell degranulation by the direct lytic factor (DLF) and phospholipase A of cobra venom.

Cobra venom, alone and in combination, on mast cell degranulation, histamine release and formation of prostaglandin-like activity (SRS-C) was studied in perfused guinea-pig lungs and in mast cell-containing rat peritoneal cell suspensions. For comparison, the effect of equivalent doses of whole cobra venom was investigated. 1. Cobra venom caused mast cell degranulation, histamine release and SRS-C formation in both systems. For comparable effects much higher doses had to be used in guine-pig lungs than in rat peritoneal cell suspensions. 2. Phase A showed little degranulation of mast cells in both systems, a limited histamine release in rat peritoneal cell suspensions and none in perfused guinea-pig lungs. It caused a considerable SRS-C formation in both, lung tissue and peritoneal cell suspensions. 3. DLF caused histamine release, SRS-C formation and mast cell degranulation in both systems; in rat peritoneal cell suspensions it acted almost as strong as equivalent doses of cobra venom, in guinea pig lungs it was much less active. 4. In rat peritoneal cell suspensions the effects of DLF and phase A in combination did not exceed the sum of their single effects. In guinea-pig lungs these two substances interacted in a potentiating synergism. It is concluded that DLF is the main cytotoxic principle of cobra venom, whereas ph-ase A alone is not cytotoxic. The difference in the synergism of DLF and ph-ase A between rat peritoneal cells and guinea-pig lungs may be due to two different actions of DLF and species differences as regards sensitivity against these actions.

Animals↗
PubMed1989

Role of peptide-leukotrienes in liver injury in mice.

The role of peptide leukotrienes (p-LTs), especially LTC4 and LTD4 in liver disease, was investigated in mice experimental liver injury models. The liver injury was induced by the injection of bacterial lipopolysaccharide (LPS) into Corynebacterium parvum pretreated mice. Carbon tetrachloride (CCl4)-induced liver injury in mice was used as a standard model. In both injury models, extensive liver parenchymal cell damage was observed by the elevation of glutamate transaminase (GOT and GPT) activity and confirmed by significant histopathological changes in the liver. Moreover, significant elevation of LTC4 in the liver was observed in both models 1 and 6 h after the onset of disease. Administration of AA-861, a selective 5-lipoxygenase inhibitor (0.5, 1, and 2 mg/kg) and LY-171883, a p-LT receptor antagonist (50 and 200 mg/kg) suppressed the elevation of serum GOT and GPT levels and histopathological changes in both experimental liver injury models. In addition, when authentic LTC4 or LTD4 was injected into the mouse, clear elevation of serum GOT and GPT and histopathological changes of the liver were observed. These results suggest that p-LTs play a role in the onset of liver diseases in mice.

Acetophenones↗
PubMed1982

Chemical studies on slow reacting substances/leukotrienes.

The family of eicasanoids, biologically active metabolites of polyunsaturated C20 fatty acids such as arachidonic acid, has recently been enlarged by the recognition of a new biosynthetic pathway leading to the leukotrienes, including the compounds described two decades ago as 'slow reacting substances'. These biologically potent substances are involved in regulation of the immune response and also as mediators in various disease states. This account presents a brief history of this field, an overview of the biological relevance of leukotrienes, and a discussion of the investigations which led to the clarification of the molecular structures, pathway of biosynthesis and total chemical synthesis of the leukotrienes, including leukotrienes A, B, C, D and E (LTA-LTE). As a result of the synthetic work these rare substances are available for the first time in pure form and in quantities sufficient for biological and medical studies. Also reviewed are recent discoveries with regard to the development of inhibitors of leukotriene biosynthesis and anti-leukotrienes.

Animals↗
PubMed1989

The effect of leukotriene antagonists, lipoxygenase inhibitors and selected standards on leukotriene-mediated allergic bronchospasm in guinea pigs.

Leukotrienes (LT) C4, D4, and E4 are major contributors to the pathobiology of human bronchial asthma. Therefore, it is likely that compounds that antagonize the action or inhibit the formation of LTs will be useful therapeutic agents. We have studied the effects of LT antagonists, 5-lipoxygenase inhibitors and selected standards in a model of LT-mediated allergic bronchospasm in guinea pigs. Sensitized animals were pretreated with mepyramine, indomethacin and propranolol to eliminate the influence of histamine, prostaglandins, thromboxanes and circulating catecholamines. In these animals, inhalation of antigen resulted in a bronchospasm consistent with a LT-mediated response that was slow in onset, of long duration and was inhibited by the selective LTD4, antagonists FPL-55712, LY-171,883 and ICI-198,615. ICI-198,615 was approximately 50-times more potent than FPL-55712 by the intravenous and intratracheal routes. However, of thirteen compounds known to inhibit 5-lipoxygenase and LT biosynthesis in vitro only phenidone, piriprost and AA-861 were active in this in vivo model. The allergic bronchospasm was inhibited by bronchodilators (e.g. PGE2, aminophylline and forskolin) and by some mast cell stabilizers, but was otherwise insensitive to other pharmacological classes of compounds including calcium channel blockers and antagonists of serotonin, acetylcholine and platelet-activating factor. This model seems useful and reasonably selective for the evaluation of new antianaphylactic compounds that are LT antagonists. The inactivity of many 5-lipoxygenase inhibitors in this model suggests they do not inhibit LT formation in vivo.

Animals↗
PubMed1981

Leucotrienes, SRS-A and the vascular manifestations of PCA.

In order to study possible mediators of the vascular manifestations of passive cutaneous anaphylaxis (PCA), several arachidonic acid metabolites were injected into guinea-pig skin. SRS-A, LTB4, LTC and LTD increased vascular permeability, responses to LTs being enhanced by PGE2. Mepyramine inhibited responses to histamine, but not those to SRS-A and LTs; the latter were inhibited by the SRS-A antagonist FPL-55712. Both mepyramine and FPL-55712 exert limited inhibitory effects on vascular permeability during PCA. Leukotrienes may contribute towards vascular permeability during PCA.

Animals↗
PubMed1976

Effects of physalaemin, a vaso-active peptide from amphibian skin, on the excitability of an identifiable molluscan giant neurone of Achatina fulica Férussac.

We examined effects of several vasoactive peptides (substance P, physalaemin, neurotensin, bradykinin, angiotensin etc.) on the excitability of molluscan giant neurones identified in the subesophageal ganglia of Achatina fulica Férussac. Of these peptides, only physalaemin showed a remarkable excitatory effect on a giant tonically autoactive neurone.

Angiotensin II↗
PubMed1980

Slow-reacting substances and their formation by a lipoxygenase pathway.

Slow-reacting substances are formed from arachidonic acid by the action of a lipoxygenase, which leads to the formation of 5-hydroperoxy, 6, 8, 11, 14 eicosatetraenoic acid. The covalent structures of SRS-A from guinea-pig lung and SRS from RBL-1 cells have been determined by protein chemical analysis and electron impact mass spectrometry of a derivative of the intact molecules. The structures of SRS-A and SRS are identical, being 5-hydroxy-6-cysteinyl-glycinyl-7, 9, 11, 14-eicosatetraenoic acid. SRSs may be formed by a combination of the metabolism of arachidonic acid by the lipoxygenase pathway and the glutathione detoxification pathway involving nucleophilic attack on 5,6-oxidoeicosatetraenoic acid.

Amino Acids↗
PubMed1978

Anti-inflammatory drug actions on allergic responses in guinea-pig skin.

Five non-steroidal anti-inflammatory drugs (indomethacin, naproxen, meclofenamic acid, feprazone and phenylbutazone: NSAIDs) and three glucocorticosteroids (dexamethasone, hydrocortisone and prednisolone) have been tested as local inhibitors of increased vascular permeability in guinea-pig skin. Lesions were induced by histamine or by antigen to evoke type I (passive cutaneous anaphylaxis), type III (reverse passive Arthus) and type IV (delayed hypersensitivity) allergic reactions. NSAIDs and glucocorticosteroids caused either weak, inconsistent inhibition or slight, high-dose inhibition of the response to histamine. None of the drugs tested showed significant inhibition of the type IV response. The NSAIDs caused dose-related inhibition of both type I and type III responses whereas glucocorticosteroids were ineffective. Maximum inhibition with the NSAIDs was never greater than 50--60% Feprazone, meclofenamic acid and indomethacin were the most potent inhibitors of histamine, PCA and Arthus responses respectively. The possible significance of the effects of these anti-inflammatory agents on vascular permeability is discussed.

Animals↗
PubMed1989

Antagonism of leukotriene receptors and administration of a 5-lipoxygenase inhibitor do not affect hypoxic vasoconstriction.

The role of leukotrienes in hypoxic vasoconstriction remains controversial. Our previous study using the lipoxygenase inhibitor BW 755C in dogs failed to show a substantive role for leukotrienes in hypoxic vasoconstriction. To clarify further the role of leukotrienes, we designed 3 protocols. In the first protocol, we examined the effects of LTD4 boluses on the pulmonary circulation in 6 anesthetized dogs. LTD4, 1 microgram/kg, (a large dose relative to other species) produced no detectable constriction of the pulmonary artery, while systemic vascular resistance increased 41 +/- 17% (SD), left atrial pressure rose 3.5 +/- 1.5 mmHg, and cardiac output fell 18 +/- 8%. Two leukotriene receptor antagonists, LY171883 and L-648051, decreased these effects by more than 50%. In the second protocol, we tested these antagonists in 7 anesthetized, paralyzed, closed-chest dogs with acute left lower lobe atelectasis. Two manifestations of hypoxic vasoconstriction were examined: shunt fraction (as an inverse indicator of regional constriction in response to local hypoxia) and the pulmonary pressor response to global alveolar hypoxia (as an index of general hypoxic vasoconstriction). During normoxia before administration of the inhibitor, shunt fraction, measured using an SF6 infusion, was 25 +/- 7%. The pulmonary pressor response to hypoxia, defined as the increase in pulmonary end-diastolic gradient (PDG) produced by 10% O2 inhalation, averaged +10.5 +/- 3.6 mmHg. The increase in pulmonary vascular resistance (PVR) with hypoxia was +2.4 +/- 1.7 mmHg/L/min. Then, during normoxia, 1 of the 2 antagonists was administered. Shunt fraction was unchanged (26 +/- 4%; p = 0.5). The pressor response to hypoxia was slightly less but remained substantial (the increase in PDG with hypoxia was +7.9 +/- 2.8 mmHg; p less than 0.05; the increase in PVR was +1.8 +/- 1.2 mmHg/L/min, p less than 0.10). In the third protocol we gave RG 5901, a relatively specific 5-lipoxygenase inhibitor, to 5 dogs with lobar atelectasis. The indices of hypoxic vasoconstriction were not affected by RG 5901. Shunt fraction was 29.5 +/- 8.1% before and 27.0 +/- 7.4% after RG 5901 (p greater than 0.05). The pressor response to hypoxia was +8.9 +/- 2.1 mmHg before and +8.7 +/- 3.7 mmHg after RG 5901 (p greater than 0.05). We conclude that in dogs, hypoxic vasoconstriction does not appear to be mediated by leukotrienes.

Acetophenones↗