References of "Journal of Pharmacology and Experimental Therapeutics"
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See detailEndothelins: functional and autoradiographic studies in guinea pig trachea
Tschirhart, Eric UL; Drijfhout, J. W.; Pelton, J. T. et al

in Journal of Pharmacology and Experimental Therapeutics (1991), 258(1), 381-7

The presence of binding sites for [125I]endothelin-1 and the contractile activities of endothelins (ETs) and sarafotoxin S6b and the endothelin fragment ET(16-21) were investigated in guinea pig trachea ... [more ▼]

The presence of binding sites for [125I]endothelin-1 and the contractile activities of endothelins (ETs) and sarafotoxin S6b and the endothelin fragment ET(16-21) were investigated in guinea pig trachea. ETs and sarafotoxin S6b (0.1-100 nM) induced potent contractile responses in guinea pig trachea with EC50 values ranging from 1.57 to 12.97 nM. Epithelium removal increased the potencies of ET-1, ET-2 and S6b, but not that of ET-3, and maximal responses to ET-1 and ET-2 were also increased. Effects of epithelium removal were partially mimicked by phosphoramidon (10 microM), an enkephalinase inhibitor, suggesting that enkephalinase (EC.3.4.24.11.) is able to degrade ET-1 and ET-2. ET-3-induced contractions were not affected by phosphoramidon. Autoradiographic studies suggested the presence of at least two specific binding sites for [125]ET-1 in guinea pig airway smooth muscle. The correlation between Kd and EC50 values suggests that the binding sites identified in the airway smooth muscle represent functional receptors for ETs. ET(16-21) and ET(16-21)-NH2 were less potent agonists than the ETs in guinea pig trachea and 10 microM ET(16-21) was unable to inhibit [125I]ET-1 binding in guinea pig airway smooth muscle. Therefore, these results suggest that the C-terminal hexapeptide of ET-1 cannot be used to classify ET receptors in guinea pig trachea. [less ▲]

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See detailActivation of rat peritoneal mast cells by substance P and mastoparan
Mousli, M.; Bronner, C.; Bueb, Jean-Luc UL et al

in Journal of Pharmacology and Experimental Therapeutics (1989), 250(1), 329-35

Incubation of rat peritoneal mast cells with substance P resulted in the transient stimulation of phosphoinositol breakdown and histamine secretion through an exocytotic process. These effects were ... [more ▼]

Incubation of rat peritoneal mast cells with substance P resulted in the transient stimulation of phosphoinositol breakdown and histamine secretion through an exocytotic process. These effects were inhibited markedly by a prior 2-hr exposure of the cells to pertussis toxin. Pertussis toxin also inhibited exocytosis induced by substance P, mastoparan and compound 48/80, but did not modify the secretory effect of the ionophore A23187. The transfer of rat peritoneal mast cells from balanced salt solution to calcium-free buffer led to a similar time-dependent decrease in their response to substance P and mastoparan. The concomitant absence of potassium from the calcium-free buffer enabled the mast cells to retain their secretory response. These data demonstrate identical dependency for calcium and monovalent ions of the secretory process elicited by substance P, mastoparan and compound 48/80. Pretreatment of mast cells with neuraminidase decreased the secretagogic effect of substance P, mastoparan and compound 48/80 without modifying the efficiency of the ionophore A23187. Thus, sialic acid residues might be involved in the initial binding of peptides and compound 48/80 to mast cells, which activate a pertussis toxin-sensitive G-protein and allows the increase in phospholipase C activity to induce exocytosis. This sequence of events might characterize the physiological pathway of mast cell activation by peptides, without necessarily requiring selective membrane receptors. [less ▲]

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See detailArachidonic acid metabolites and airway epithelium-dependent relaxant factor
Tschirhart, Eric UL; Frossard, N.; Bertrand, C. et al

in Journal of Pharmacology and Experimental Therapeutics (1987), 243(1), 310-6

Exogenous arachidonic acid (10(-8) to 10(-4) M) contracted epithelium-free guinea pig tracheal strips. Intact tracheal strips were contracted slightly by low concentrations of arachidonic acid (10(-8) to ... [more ▼]

Exogenous arachidonic acid (10(-8) to 10(-4) M) contracted epithelium-free guinea pig tracheal strips. Intact tracheal strips were contracted slightly by low concentrations of arachidonic acid (10(-8) to 10(-5) M), but higher concentrations relaxed them. In contrast, when tracheal strips were precontracted with histamine or carbachol, exogenous arachidonic acid had no effect on epithelium-free preparations but induced concentration-dependent (10(-8) to 10(-4) M) relaxation of intact tracheal strips. The effects of arachidonic acid both in epithelium-free and epithelium-containing trachea were blocked by either indomethacin (10(-6) M) or aspirin (10(-4) M). Studies on the effects of exogenous arachidonic acid, performed with a "sandwich protocol," demonstrated that the postulated airway epithelium-dependent relaxant factor released by an intact tracheal strip relaxes an adjacent epithelium-free strip in the same organ bath. This relaxation is antagonized by indomethacin suggesting the involvement of a cyclooxygenase product in this phenomenon. Comparison of concentration-response curves for contractile agonists in epithelium-free preparations and in one containing epithelium suggests the mobilization of airway epithelium-dependent relaxant factor by histamine but not by carbachol. The effects of cyclooxygenase and lipoxygenase inhibitors indicated that both relaxant and contractile arachidonic acid metabolites are generated by epithelial and nonepithelial cells alike in response to contractile agonists. [less ▲]

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