TY - JOUR
T1 - Regulation of mast cell histamine release by neurotensin
AU - Rossie, Sandra S.
AU - Miller, Richard J.
N1 - Funding Information:
Supported by PHS grant DA 02121 and a grant from the National Foundation for lleitis and Colitis. RJM is an Alfred P. Sloan Fellow. SSR is supported by PHS grant GM 07151.
PY - 1982/8/9
Y1 - 1982/8/9
N2 - Neurotensin (NT), a neuropeptide found both centrally and peripherally, stimulated release of histamine from rat peritoneal mast cells in a dose-dependent manner. Release was evident by 10 nM and reached a plateau of 15-20% total cellular histamine by 10-7-10-6 M NT. Optimal conditions for stimulation occurred at pH 6.5-7.5, 37°C and at calcium concentrations of ≤1 mM. Release was complete within 2 minutes of peptide addition. Studies of histamine release by NT analogues indicated that the C-terminus is the biologically active portion of the molecule in this system, as is true of all other systems responsive to NT (1). D-Trp11-NT, which acts as a NT antagonist in several peripheral NT-sensitive tissues (2,3), also inhibited NT action on mast cells. Manipulations involving Ca2+ availability suggest that the mechanism of NT stimulation may involve use of intracellular Ca2+ to a greater extent than extracellular Ca2+. Lowering the extracellular Ca2+ concentration or blocking influx of extracellular Ca2+ with lanthanum (La3+), had little effect on NT-induced release, whereas Ca2+ depletion by treatment with ethylenediaminetetracetic acid (EDTA) or blockade of intracellular Ca2+ mobilization by N,N-(diethylamino)octyl 3,4,5-trimethoxybenzoate (TMB-8), inhibited the response to NT. Increasing cellular levels of adenosine 3′, 5′-cyclic monophosphate (cAMP), by treatment with 8-bromo-cAMP or stimulation with prostaglandin E2 (PGE2) in the presence of isobutylmethylxanthine (IBMX), served to reduce histamine release by NT, indicating that cAMP may play a role in NT stimulation.
AB - Neurotensin (NT), a neuropeptide found both centrally and peripherally, stimulated release of histamine from rat peritoneal mast cells in a dose-dependent manner. Release was evident by 10 nM and reached a plateau of 15-20% total cellular histamine by 10-7-10-6 M NT. Optimal conditions for stimulation occurred at pH 6.5-7.5, 37°C and at calcium concentrations of ≤1 mM. Release was complete within 2 minutes of peptide addition. Studies of histamine release by NT analogues indicated that the C-terminus is the biologically active portion of the molecule in this system, as is true of all other systems responsive to NT (1). D-Trp11-NT, which acts as a NT antagonist in several peripheral NT-sensitive tissues (2,3), also inhibited NT action on mast cells. Manipulations involving Ca2+ availability suggest that the mechanism of NT stimulation may involve use of intracellular Ca2+ to a greater extent than extracellular Ca2+. Lowering the extracellular Ca2+ concentration or blocking influx of extracellular Ca2+ with lanthanum (La3+), had little effect on NT-induced release, whereas Ca2+ depletion by treatment with ethylenediaminetetracetic acid (EDTA) or blockade of intracellular Ca2+ mobilization by N,N-(diethylamino)octyl 3,4,5-trimethoxybenzoate (TMB-8), inhibited the response to NT. Increasing cellular levels of adenosine 3′, 5′-cyclic monophosphate (cAMP), by treatment with 8-bromo-cAMP or stimulation with prostaglandin E2 (PGE2) in the presence of isobutylmethylxanthine (IBMX), served to reduce histamine release by NT, indicating that cAMP may play a role in NT stimulation.
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U2 - 10.1016/0024-3205(82)90478-7
DO - 10.1016/0024-3205(82)90478-7
M3 - Article
C2 - 6182435
AN - SCOPUS:0020374340
SN - 0024-3205
VL - 31
SP - 509
EP - 516
JO - Life Sciences
JF - Life Sciences
IS - 6
ER -