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Biomedical subjects

M N Samhoun

Publications and source records attributed to M N Samhoun.

At least 19 recordsLinked to original sources
PubMed1991

Effects of vasoactive intestinal peptide, helodermin and galanin on responses of guinea-pig lung parenchyma to histamine, acetylcholine and leukotriene D4.

1. The effect of vasoactive intestinal peptide (VIP) was studied on the contractile response of guinea-pig lung parenchymal strips (GPP) induced by bronchoconstrictor agonists, such as leukotriene D4 (LTD4), histamine and acetylcholine (ACh). This effect of VIP was compared with helodermin, a peptide that is structurally related to VIP, and galanin, another neuropeptide that is thought to co-exist with VIP. 2. VIP (10 nM) induced a potent and reversible inhibition of the contractions of GPP induced by LTD4 (1-30 pmol) but did not affect those due to ACh (1-100 nmol) or histamine (1-30 nmol). A ten fold higher concentration of VIP (100 nM) did not further inhibit LTD4-induced responses or reduce those induced by histamine or ACh. 3. Helodermin (10 nM) had a similar inhibitory effect on contractions of GPP induced by LTD4 (3-30 pmol) but did not affect contractions induced by histamine (1-10 nmol). 4. Indomethacin (2.8 microM) and salbutamol (10 nM) significantly reduced responses elicited by LTD4 and histamine but not those due to ACh. A ten fold higher concentration of salbutamol (100 nM) further inhibited the contractions due to LTD4 and histamine and at this concentration responses induced by ACh were inhibited. 5. VIP (10 nM) and helodermin (10 nM) significantly reduced the LTD4-induced release of thromboxane A2 (TXA2), measured as TxB2 by radioimmunoassay, from GPP. The smaller release of TxA2 induced by histamine was not significantly reduced in the presence of VIP. 6. In comparative studies, galanin (10-100 nM) did not affect contractions of GPP induced by either LTD4, histamine or ACh. In contrast to VIP and helodermin, both at 0.1-3 nmol, which induced doserelated relaxations of guinea-pig trachea, galanin was inactive on this preparation in doses of up to 3 nmol.7. In conclusion, our results show that contractions of GPP induced by LTD4 are more sensitive to inhibition by VIP and helodermin than are contractions due to histamine or ACh. This inhibition appears to be associated with the different contribution of released TxA2 to contractions evoked by the agonists. VIP and helodermin inhibit the cyclo-oxygenase-dependent component of the LTD4-induced response, as in the case of indomethacin.

Acetylcholine↗
PubMed1990

Relaxations of guinea-pig isolated trachea induced by platelet-activating factor are epithelial-dependent and are antagonised by WEB 2086.

Platelet-activating factor (PAF, 10-1000 pmol) induced dose-dependent relaxations of the basal tone of superfused strips of epithelium-intact guinea-pig trachea. Indomethacin (1.4 microM) completely inhibited and WEB 2086 (1 and 10 nM) effectively antagonised these relaxations. Following epithelial removal PAF evoked a single contraction. These results show that the PAF-induced relaxations of guinea-pig trachea are dependent on an intact epithelial layer and are mediated by a cyclo-oxygenase product.

Albuterol↗
PubMed1990

The role of the epithelium in modulating the responses of guinea-pig trachea induced by bradykinin in vitro.

1. The effect of removing the epithelium on the responses of the guinea-pig isolated trachea (GPT) to bradykinin (BK) and prostaglandin E2 (PGE2) was investigated. 2. BK (3 pmol-10 nmol) induced dose-related relaxations of the intact (with epithelium), and contracted the rubbed (without epithelium) preparation of GPT. Similar responses were also obtained with PGE2 (0.3-3.0 nmol). 3. Indomethacin (1.4 microM) modified the BK-induced response of intact GPT, from a relaxation to a contraction, but inhibited the BK-induced contraction of the rubbed GPT. 4. There was a significant increase in PGE2 release from the intact GPT following stimulation with BK. 5. Removal of the epithelium from the GPT significantly reduced both basal and BK-induced generation of PGE2. 6. The induction of tone in the rubbed GPT by addition of acetylcholine (ACh) caused BK and PGE2 (0.3 nmol-3 nmol) to produce relaxations of the tissue. 7. Salbutamol (10(-8) M-10(-6) M) reduced the relaxations induced by BK on intact GPT, in a concentration-dependent manner. 8. These results suggest that both tone and an epithelial-dependent cyclo-oxygenase mechanism are important in modulating BK-induced responses of GPT.

Acetylcholine↗
PubMed1989

Pharmacological profile of leukotrienes E4, N-acetyl E4 and of four of their novel omega- and beta-oxidative metabolites in airways of guinea-pig and man in vitro.

1, The biological effects of metabolites of leukotriene E4 (LTE4) i.e. N-acetyl LTE4 (N-AcLTE4), 20-COOH-LTE4, 20-COOH-N-AcLTE4, as well as 18-COOH-19,20-dinor-LTE4 (dinor-LTE4) and 16-COOH-17,18,19,20-tetranor-14,15-dihydro-LTE4 (tetranor-LTE4) were investigated on superfused strips of guinea-pig trachea (GPT) and lung parenchyma (GPP) in vitro. 2. The actions of LTE4 were studied in isolated, superfused strips of human lung parenchyma (HP) and bronchus (HBr), in comparison with LTD4 and histamine. Effects of N-AcLTE4, the 20-carboxy metabolites, dinor-LTE4 and tetranor-LTE4 were also investigated in HBr. 3. N-AcLTE4 (0.1-10 nmol) induced dose-related contractions of GPT and was approximately 100 times less active than LTD4 (3-100 pmol). 4. In GPP, N-AcLTE4 (0.01-3 nmol) was equiactive with LTE4 (0.01-1 nmol) and approximately one order of magnitude less active than LTD4 (1-300 pmol). Contractions caused by N-AcLTE4 and LTE4 were very similar and approximately twice as sustained as those due to LTD4. 5. LTE4 (0.1-30 nmol) contracted strips of HP and HBr and was about 2-3 orders of magnitude less active than LTD4. As in GPP, the effect of LTE4 was more protracted than that of LTD4. Actions of N-AcLTE4 were similar to those of LTE4 in HBr. 6. 20-carboxy-LTE4, 20-carboxy-N-AcLTE4, dinor-LTE4 and tetranor-LTE4, all at 0.3-30 nmol, were inactive in GPT, GPP and HBr. 7. Indomethacin (2.8 microM) potentiated the effect of N-AcLTE4 in GPT, inhibited its contraction in GPP but did not affect that due to LTE4 in either HP or HBr. FPL 55712 (1.9 microM) antagonised leukotriene-induced contractions in GPT, GPP and HBr. 8. In conclusion, the metabolism of LTD4 to LTE4 or N-AcLTE4 may represent a detoxification but not an inactivation of cysteinyl-containing leukotrienes, since both metabolites still retain considerable biological activity in guinea-pig and human airways in vitro. However, further metabolism of LTE4 and N-AcLTE4 appears to result in inactivation of leukotrienes.

Animals↗
PubMed1987

Leukotrienes.

Explore the source record for details and available documents.

Animals↗
PubMed1984

The combined use of isolated strips of guinea-pig lung parenchyma and ileum as a sensitive and selective bioassay for leukotriene B4.

The biological effects of leukotriene (LT)B4 were compared, on a molar basis, with those of LTC4, LTD4, LTE4, 5-hydroxyeicosatetraenoic acid (5-HETE), PGD2, PGE1, PGE2, PGF2 alpha, PGI2, 6-oxo-PGF1 alpha, bradykinin (BK) and angiotensin II (Ang II) on isolated strips of guinea-pig lung parenchyma (GPP) and ileum smooth muscle (GPISM) superfused in series. LTB4 was similar to LTC4 and LTD4 on GPP, in relation to potency and contractions induced, but differed from LTE4 in being ten times more active and causing contractions of a much shorter duration of action on this tissue. However, unlike the other LTs, LTB4 produced contractions which were resistant to FPL 55712 (1.9 microM) and, when given repeatedly, caused tachyphylaxis in GPP. LTB4 was considerably more active on GPP than the other substances investigated. Further, PGD2, PGF2 alpha and PGI2 contracted GPP, the order of potency being PGD2 greater than PGF2 alpha approximately equal to PGI2, whereas PGE1 and PGE2 relaxed this tissue. In contrast to all other agonists tested which contracted GPISM, LTD4 displaying the highest activity, LTB4 was inactive on this tissue. 5-HETE and 6-oxo-PGF1 alpha were inactive on both GPP and GPISM. On the basis of differential effects of LTB4 on GPP and GPISM, this assay represents a simple and selective means to distinguish LTB4-like materials from other naturally-occurring substances likely to be generated in inflammatory fluids.

Angiotensin II↗
PubMed1984

Actions and interactions of lipoxygenase and cyclo-oxygenase products in respiratory and vascular tissues.

Actions of leukotrienes (LTs) B4, C4, D4 and E4 were found to be largely mediated via formation of cyclo-oxygenase products in guinea-pig isolated perfused lung and parenchymal strips. In contrast, LTs exerted a direct contractile effect on human isolated parenchymal and bronchial strips. An LT-like substance which had similar biological actions to LTD4 was generated from porcine and guinea-pig vascular tissue. The highest concentration of this material was formed by coronary and pulmonary arteries and the surrounding adventitia, as well as from the lung parenchyma.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1982

Slow reacting substances (leukotrienes): enzymes involved in their biosynthesis.

Slow reacting substances (leukotrienes C4, D4, E4) are synthesized in vivo by a combination of two previously unrelated pathways: lipoxygenase oxygenation of arachidonic acid and the glutathione detoxification pathway. Enzymes involved in the latter pathway (glutathione transferase [RX: glutathione R-transferase, EC 2.5.1.18]; gamma-glutamyltransferase [(5-glutamyl)-peptide: amino acid 5-glutamyltransferase, EC 2.3.2.2] ) have been investigated in guinea pig lung and rat basophilic leukemia (RBL-1) cells. We report data on levels of enzymic activity both before and during the release of slow reacting substances. Both glutathione transferase and gamma-glutamyltransferase are present in significant quantities in guinea pig lung and RBL-1 cells. A model for the changes in gamma-glutamyltransferase during leukotriene release is proposed for the cell line, and differences from the guinea pig lung system are reported. Leukotriene C4 is converted to the more potent leukotriene D4 by the action of gamma-glutamyltransferase on guinea pig ileum during bioassay. gamma-Glutamyltransferase may represent a control feature in the biosynthesis of leukotriene D4, and thus be involved in leukotriene-induced bronchoconstriction in the lung.

Animals↗
PubMed1982

Generation of leukotriene B4, its all trans isomers and 5-hydroxyeicosatetraenoic acid by rat basophilic leukaemia cells.

1 When rat basophilic leukaemia (RBL-1) cells were incubated for 4 min, in the presence of arachidonic acid (AA) and calcium ionophore A23187, three isomers of leukotriene (LT) B4 and 5-hydroxyeicosatetraenoic acid (5-HETE) were generated. 2 The isomers of LTB4 separated by reverse phase high pressure liquid chromatography (h.p.l.c.) were found to be 5 (s)-dihydroxy-6, 14-trans-8,10-trans-eicosatetraenoic acid: 5(S), 12(R)-dihydroxy-6,14-trans-8,10-trans-eicosatetraenoic acid and 5(S),12(R)-dihydroxy-6,14-cis-8,10-trans-eicosatetraenoic acid or LTB4. 3 5(S), 12(R)-cis, trans, trans-LTB4 produced by RBL-1 cells caused aggregation of rat polymorphonuclear leucocytes (PMNs). Its other two isomers (5(S), 12(S)-all trans-LTB4; 5(S), 12-(R)-all trans-LTB4) were much less active and 5-HETE was found to be inactive. 4 5(S), 12(R)-cis, trans, trans-LTB4 formed from RBL-1 cells contracted guinea-pig parenchymal strips (GPPs) and was indistinguishable from synthetic 5(S), 12(R)-cis, trans, trans-LTB4. The other two isomers of LTB4. i.e. 5(S), 12(S)-all trans-LTB4 and 5(S), 12(R)-all trans-LTB4 as well as 5-HETE were inactive on GPP. 5 RBL-1 LTB4 was equipotent with LTD4. in most experiments, in contracting GPP but had no activity on guinea-pig ileum smooth muscle (GPISM). 6 RBL-1 cells contain the enzyme systems necessary for generating LTB4 as well as the leukotriene(s) with amino acid residues at C-6.

Animals↗
PubMed1982

Stimulation of arachidonic acid metabolism and generation of thromboxane A2 by leukotrienes B4, C4 and D4 in guinea-pig lung in vitro.

1 Leukotriene C4 (LTC4), LTD4, slow-reacting substance of anaphylaxis (SRS-A) (from guinea-pig lung), bradykinin (Bk) and arachidonic acid (AA) release thromboxane A2 (TxA2) and prostaglandin-like materials from guinea-pig isolated perfused lungs. 2 Release of TxA2 induced by LTC4 and LTD4 is inhibited by a thromboxane synthetase inhibitor, imidazole (2.9 mM). 3 Mepacrine (200 microM), a phospholipase inhibitor, inhibits release of TxA2 and prostaglandin-like materials caused by SRS-A and Bk but not that due to exogenous AA 4 Leukotrienes B4, C4 and D4 are approximately equipotent in inducing dose-related contractions of guinea-pig parenchymal strips (GPPs). 5 Leukotriene-induced contractions of GPPs are greatly inhibited by imidazole (2.9 mM), carboxyheptylimidazole (24 microM) and mepacrine (400 microM). 6 FPL 55712 (1.9 microM), the SRS-A antagonist, blocks contractions of GPPs induced by LTC4 and LTD4 but not those due to LTB4 or Bk. 7 Tachyphylaxis to LTB4 occurs in GPPs but not to LTC4 or LTD4. 8 These results suggest that in guinea-pig lung in vitro, LTB4, LTC4 and LTD4 activate a phospholipase with subsequent generation of cyclo-oxygenase products of which TxA2 plays an important role.

Animals↗
PubMed1981

The mechanism of action of leukotrienes C4 and D4 in guinea-pig isolated perfused lung and parenchymal strips of guinea pig, rabbit and rat.

The biological actions of pure slow-reacting substance of anaphylaxis (SRS-A) from guinea-pig lung, pure slow-reacting substance (SRS) from rat basophilic leukaemia cells (RBL-1) and synthetic leukotrienes C4 (LTC4) and D4 (LTD4) have been investigated on lung tissue from guinea pig, rabbit and rat. In the guinea pig, the leukotrienes released cyclo-oxygenase products from the perfused lung and contracted strips of parenchyma. The effects of SRS-A, SRS and LTD4 were indistinguishable. LTC4 and LTD4 had similar actions although LTD4 was more potent than LTC4. Indomethacin (1 microgram/ml) inhibited the release of cyclo-oxygenase products from perfused guinea-pig lung and caused a marked reduction in contractions of guinea-pig parenchymal strips (GPP) due to LTC4 and LTD4. The residual contraction of the GPP was abolished by FPL 55712 (0.5 - 1.0 microgram/ml). It appears, therefore, 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). In rabbit and rat lung, however, SRS-A, SRS and the leukotrienes were much less potent in contracting parenchymal strips and there was little evidence of the release of cyclo-oxygenase products. FPL 55712 at a concentration of 1 microgram/ml failed to antagonise leukotriene-induced contractions.

Animals↗