References of "Naunyn-Schmiedeberg's Archives of Pharmacology"
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See detailThe M2 muscarinic receptor antagonist methoctramine activates mast cells via pertussis toxin-sensitive G proteins
Chahdi, A.; Daeffler, L.; Bueb, Jean-Luc UL et al

in Naunyn-Schmiedeberg's Archives of Pharmacology (1998), 357(4), 357-62

Methoctramine, a selective M2 muscarinic cholinergic receptor antagonist, has been reported to activate phosphoinositide breakdown at high concentrations. Its polyamine structure suggests a putative ... [more ▼]

Methoctramine, a selective M2 muscarinic cholinergic receptor antagonist, has been reported to activate phosphoinositide breakdown at high concentrations. Its polyamine structure suggests a putative activation of guanine nucleotide-binding proteins (G proteins). Incubation of methoctramine with rat peritoneal mast cells resulted in a dose-dependent noncytotoxic histamine release, with an EC50 of 20 microM and a maximum effect at 1 mM. Atropine, pirenzepine and HHSiD neither inhibited methoctramine-induced histamine release nor stimulated histamine release. Histamine release and inositol phosphates generation induced by methoctramine were both inhibited by pertussis toxin pretreatment. Benzalkonium chloride, a selective inhibitor of histamine secretion induced by basic secretagogues, inhibited the secretory response to methoctramine. [p-Glu5, D-Trp7,9,l0]-SPs5-11 (GPAnt-2), a well-characterized antagonist of G proteins, blocked the methoctramine-induced histamine release when the antagonist was allowed to reach its intracellular target by streptolysin O-permeabilization. The response to methoctramine was prevented by the hydrolysis of sialic acid residues of the cell surface by neuraminidase. The response of mast cells was restored by permeabilization of the plasma membrane. These results demonstrate that methoctramine, following its entry into the cell and the involvement of pertussis toxin-sensitive G proteins, activates phosphoinositide hydrolysis leading to mast cell exocytosis. [less ▲]

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See detailEvidence for the involvement of calcitonin gene-related peptide in the epithelium-dependent contraction of guinea-pig trachea in response to capsaicin
Tschirhart, Eric UL; Bertrand, C.; Theodorsson, E. et al

in Naunyn-Schmiedeberg's Archives of Pharmacology (1990), 342(2), 177-81

Capsaicin (10(-9) to 10(-5) M) contracted guinea-pig tracheal strips. Epithelium-containing tracheal strips developed a maximum active tension which was significantly higher than that observed in ... [more ▼]

Capsaicin (10(-9) to 10(-5) M) contracted guinea-pig tracheal strips. Epithelium-containing tracheal strips developed a maximum active tension which was significantly higher than that observed in epithelium-free strips. Anti-CGRP (calcitonin gene-related peptide) serum blocked the epithelium-dependent potentiation of the capsaicin-induced contraction in the intact tracheal strips, without affecting the response of the epithelium-free strips. This result suggests the occurrence of an epithelium-dependent release of CGRP. This same serum markedly reduced the contraction induced by exogenous rat CGRP in both intact and epithelium-free tracheal strips. In epithelium-free tracheal strips, capsaicin-induced contraction was abolished by spantide (10(-6) and 10(-5) M), a substance P antagonist, but, in intact tracheal strips, spantide did not abolish the capsaicin-induced contraction, showing that both CGRP and substance P release are directly induced by capsaicin. Moreover, the contractile responses to rat CGRP of intact tracheal strips from guinea pig suggest that CGRP itself might be able to release a contracting factor from the airway epithelium. Therefore, CGRP originating from the airway epithelium may play a major role in the control of airway smooth muscle tone. [less ▲]

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See detailContractile activity of the N-acylated C-terminal part of substance P7-11 in guinea pig trachea. Effect of epithelium removal
Tschirhart, Eric UL; Schmitt, P.; Bertrand, C. et al

in Naunyn-Schmiedeberg's Archives of Pharmacology (1989), 340(1), 107-10

Substance P, neurokinin A, neurokinin B, and N-acylated pentapeptide X-Phe-Phe-Gly-Leu-Met-NH2 analogs of substance P7-11 were tested for their spasmogenic activities in intact or in epithelium-denuded ... [more ▼]

Substance P, neurokinin A, neurokinin B, and N-acylated pentapeptide X-Phe-Phe-Gly-Leu-Met-NH2 analogs of substance P7-11 were tested for their spasmogenic activities in intact or in epithelium-denuded tracheal strips from guinea pig. Epithelium removal enhanced the efficacies and potencies relative to substance P of all the peptides tested in guinea pig trachea. In epithelium-containing preparations, the presence of a cyclic substituent (o-hydroxyphenyl-acetyl, p-hydroxyphenyl-acetyl, pyroglutamyl) in Phe7 greatly enhanced the potency and efficacy compared to substance P. These substitutions were twice as active as neurokinin A itself. The presence of an aliphatic chain (non-protected and t-butyloxycarbonyl-protected aminopropyl and aminocaproyl) in Phe7 also improved the potency and the efficacy of the synthetic peptides. The aliphatic substituents could favour an increase in local concentration of the peptides in the vicinity of the receptor(s) allowing a more effective ligand-receptor interaction. Thus, lipophilicity could be determinant in the potency of the peptides in intact guinea pig trachea. In epithelium-denuded tracheal strips from guinea pig, all the synthetic peptides were more effective than substance P but less active than neurokinin A which probably reflects the presence of the NK2 receptor subtype, which may be predominant in this type of epithelium-denuded preparation. Our results suggest that hydrophobicity plays a strong role in the interaction of the peptides, namely substance P and its analogues with the membrane and possibly the receptors themselves. [less ▲]

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See detailChanges in the arterial blood pressure increase the release of endogenous histamine in the hypothalamus of anaesthetized cats
Philippu, Athineos; Hagen, Rolf; Dietl, Hans et al

in Naunyn-Schmiedeberg's Archives of Pharmacology (1983), 323(2), 162-167

Detailed reference viewed: 90 (0 UL)