Blockade of mast cell histamine secretion in response to neurotensin by SR 48692, a nonpeptide antagonist of the neurotensin brain receptor

1 Pretreatment of rat isolated mast cells with SR 48692, a nonpeptide antagonist of the neurotensin (NT) receptor, prevented histamine secretion in response to NT. 2 This inhibition was rapid in onset (∽1 min) and dependent upon the concentration of SR 48692 (IC50 ∽1–10 nM). 3 SR 48692 (l‐1000 nM) d...

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Bibliographic Details
Published in:British journal of pharmacology 1995-04, Vol.114 (7), p.1466-1470
Main Authors: Miller, Lisa A., Cochrane, David E., Carraway, Robert E., Feldberg, Ross S.
Format: Article
Language:English
Subjects:
Animals
antagonist
Biological and medical sciences
Bradykinin - pharmacology
Cell receptors
Cell structures and functions
Dose-Response Relationship, Drug
Fundamental and applied biological sciences. Psychology
Histamine - metabolism
Histamine Release - drug effects
histamine secretion
Male
mast cell
Mast Cells - drug effects
Molecular and cellular biology
Neuropeptide receptors
Neurotensin
Neurotensin - pharmacology
neurotensin receptor
Pyrazoles - pharmacology
Quinolines - pharmacology
Rats
Rats, Sprague-Dawley
SR 48692
Substance P - pharmacology
Time Factors
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Summary:1 Pretreatment of rat isolated mast cells with SR 48692, a nonpeptide antagonist of the neurotensin (NT) receptor, prevented histamine secretion in response to NT. 2 This inhibition was rapid in onset (∽1 min) and dependent upon the concentration of SR 48692 (IC50 ∽1–10 nM). 3 SR 48692 (l‐1000 nM) did not inhibit histamine secretion elicited by substance P, bradykinin or compound 48/80, or by anti‐IgE stimulation of sensitized mast cells. 4 When SR 48692 was injected intradermally (5 pmol in 50 μl) into anaesthetized rats, 15 min before the intradermal injection of NT, it reduced the effect of NT on vascular permeability. 5 When injected intravenously, SR 48692 attenuated the effects of NT on haematocrit and blood stasis. 6 These results demonstrate that SR 48692 selectively antagonizes the actions of NT on rat isolated mast cells as well as mast cells in vivo. Given the demonstrated specific interaction of SR 48692 with receptors for NT in brain, our results suggest the presence of specific NT receptors on mast cells.
ISSN:0007-1188
1476-5381
DOI:10.1111/j.1476-5381.1995.tb13371.x