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The effects of leukotrienes C4 (LTC4) and D4 (LTD4) on the secretion by human bronchial mucosa of [14C]glucosamine-labeled, trichloro-acetic acid/phosphotungstic acid-precipitable glycoprotein and lysozyme were evaluated in vitro. LTC4 and LTD4, in the concentration range of 0.16 to 1600 nM, induced a dose-related increase in the release of radiolabeled glycoprotein, but not of lysozyme. This secretagogue effect was selective for high molecular weight glycoproteins of about 2-5 x 10(6) daltons, and the median effective concentrations (EC50) of LTC4 of 9.4 x 10(-9) M and of LTD4 of 2.44 x 10(-8) M, indicate that these leukotrienes are approximately 100-fold more potent than the cholinergic agonist methacholine. Incubation of [14C]glucosamine-labeled bronchial mucosal explants with LTC4 or LTD4 for six sequential 15-min periods revealed a rapid, progressive decrement in glycoprotein release, compatible with stimulatory action on secretion rather than augmentation of the rate of glycoprotein synthesis. This interpretation is also consistent with the finding that the specific activity (ratio of bound radiolabel: protein content) of the macromolecular glycoprotein secreted by the explants is not changed with stimulation of release by the leukotrienes. Based upon the activity of synthetic leukotriene analogs, the specific C-6 chirality of the sulfidopeptide of LTD4, the presence of a hydroxyl at C-5 and the presence of eicosanoid carbons 9-20 were of no importance for secretagogue activity. These findings contrast with the stereochemical requirements for the spasmogenic response to sulfidopeptide leukotrienes and suggest that leukotriene-induced secretion is not likely to be mediated via a specific receptor.
S J Coles, and
K H Neill, and
L M Reid, and
K F Austen, and
Y Nii, and
E J Corey, and
R A Lewis
November 1992,
British journal of clinical pharmacology,
S J Coles, and
K H Neill, and
L M Reid, and
K F Austen, and
Y Nii, and
E J Corey, and
R A Lewis
December 1995,
Rhinology,
S J Coles, and
K H Neill, and
L M Reid, and
K F Austen, and
Y Nii, and
E J Corey, and
R A Lewis
April 1994,
The American journal of physiology,
S J Coles, and
K H Neill, and
L M Reid, and
K F Austen, and
Y Nii, and
E J Corey, and
R A Lewis
October 1987,
Prostaglandins, leukotrienes, and medicine,
S J Coles, and
K H Neill, and
L M Reid, and
K F Austen, and
Y Nii, and
E J Corey, and
R A Lewis
May 1987,
The Journal of surgical research,
S J Coles, and
K H Neill, and
L M Reid, and
K F Austen, and
Y Nii, and
E J Corey, and
R A Lewis
July 1988,
Japanese journal of pharmacology,
S J Coles, and
K H Neill, and
L M Reid, and
K F Austen, and
Y Nii, and
E J Corey, and
R A Lewis
November 1980,
Acta physiologica Scandinavica,
S J Coles, and
K H Neill, and
L M Reid, and
K F Austen, and
Y Nii, and
E J Corey, and
R A Lewis
August 1985,
The American review of respiratory disease,
S J Coles, and
K H Neill, and
L M Reid, and
K F Austen, and
Y Nii, and
E J Corey, and
R A Lewis
April 1982,
The Journal of pharmacology and experimental therapeutics,
S J Coles, and
K H Neill, and
L M Reid, and
K F Austen, and
Y Nii, and
E J Corey, and
R A Lewis
April 1998,
Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery,
