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M N Samhoun

Publications and source records attributed to M N Samhoun.

14 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.

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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↗
PubMed1980

Slow-reacting substances and their structural elucidation.

For more than forty years since their discovery, the structure of a group of closely related materials known collectively as slow-reacting substances has been unknown. These substances are released from a variety of tissues in response to immunological or non-immunological stimulation. A slow-reacting substance is believed to be implicated in hypersensitivity reactions such as asthma; in order to fully understand its bronchoconstrictor role, the structural elucidation of these materials has been a necessary (albeit difficult) task. Studies on both immunologically generated slow-reacting substance of anaphylaxis (SRS-A) and other slow-reacting substances (SRSs) have indicated a precursor role for arachidonic acid in their biosynthesis; this, coupled with enzymic and chemical activity destruction data, gave an insight into the structure of these moieties. In order to define the structure of these materials homogeneous SRS-A was required; a purification scheme was developed relying on the high resolution separative capability of reverse-phase high pressure liquid chromatography, resulting in extensively purified SRS-A. It was then possible to demonstrate that SRS-A possessed a characteristic ultraviolet spectrum, allowing us for the first time to define a major structural moiety in the molecule (conjugated triene). To complement studies on, and to act as a model for the more pathologically relevant SRS-A, a slow-reacting substance was produced from rat basophilic leukaemia (RBL-1) cells. The structure of this biologically active species has been determined by mass spectrometric examination of the intact molecule as a derivative, together with analytical protein chemical studies, and shown to be the novel peptidolipid 5-hydroxy-6-cysteinylglycinyl-7,9,11,14-eicosatetraenoic acid.

Animals↗
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↗
PubMed1980

Slow reacting substances (SRSs): the structure identification of SRSs from rat basophil leukaemia (RBL-1) cells.

Slow Reacting Substances have been produced from RBL-l cells by calcium ionophore A23187 and purified to homogeneity by high pressure liquid chromatography (HPLC). The structure of the major biologically active species has been determined by mass spectrometric examination of the intact molecule as a derivative, together with amino-acid analysis and sequence determination. The characteristic triene chromophore which we originally identified in immunologically generated SRS-A is present in RBL-l SRS, and we determine the structure of this SRS as the thio-substituted dipeptide, 5-hydroxy-6-cysteinylglycinyl-7,9,11,14-eicosatetraenoic acid.

Amino Acid Sequence↗