Interleukin-4 modulates cholinergic neural control of mouse small intestinal longitudinal muscle.
Interleukin-4 contributes to expulsion of certain gastrointestinal parasites and causes intestinal mucosal mastocytosis. Because mast cell-derived mediators are spasmogenic, potentially causing parasitic expulsion, we investigated the effect of interleukin-4 on smooth muscle and the mast cell and mediator dependency of this effect. BALB/c, mast cell-deficient W/Wv mice, 5-lipoxygenase-efficient mice, and their littermate controls were injected with interleukin-4-anti-interleukin-4 antibody complexes that chronically increase serum interleukin-4 levels. Mid-small intestinal segments, hung longitudinally in organ baths, were stimulated electrically or by agonists. The cholinergic response to electrical field stimulation was significantly increased by interleukin-4 treatment in BALB/c but not W/Wv mice. The enhanced cholinergic contraction was not due to increased acetylcholine responsiveness but was dependent on leukotriene D4, since it was reversed by leukotriene D4 receptor antagonism, and not observed in 5-lipoxygenase knock-out mice. Leukotriene D4 responsiveness was unaffected by interleukin-4 treatment. We conclude that interleukin-4 amplifies cholinergic excitation through a mast cell and leukotriene D4-dependent mechanism.
Goldhill
J
J
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20815, USA.
Morris
S C
SC
Maliszewski
C
C
Urban
J F
JF
Funk
C D
CD
Finkelman
F D
FD
Shea-Donohue
T
T
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000172:deficiency; D004558:Electric Stimulation; D005260:Female; D006632:Histamine / Q000494:pharmacology / Q000502:physiology; D015847:Interleukin-4 / Q000494:pharmacology*; D007421:Intestine, Small / Q000294:innervation*; D017998:Leukotriene D4 / Q000494:pharmacology / Q000502:physiology; D008297:Male; D008407:Mast Cells / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D009130:Muscle, Smooth / Q000294:innervation*; D010275:Parasympathetic Nervous System / Q000187:drug effects* / Q000502:physiology*
D015847:Interleukin-4; D017998:Leukotriene D4; D006632:Histamine; D001094:Arachidonate 5-Lipoxygenase; D000109:Acetylcholine