Differential role of tachykinin NK3 receptors on cholinergic excitatory neurotransmission in the mouse stomach and small intestine.
OBJECTIVE
Tachykinin NK(3) receptors are widely expressed in the mouse gastrointestinal tract but their functional role in enteric neuromuscular transmission remains unstudied in this species. We investigated the involvement of NK(3) receptors in cholinergic neurotransmission in the mouse stomach and small intestine.


METHODS
Muscle strips of the mouse gastric fundus and ileum were mounted in organ baths for tension recordings. Effects of NK(3) agonists and antagonists were studied on contractions to EFS of enteric nerves and to carbachol.


RESULTS
EFS induced frequency-dependent tetrodotoxin-sensitive contractions, which were abolished by atropine. The cholinergic contractions to EFS in the stomach were enhanced by the NK(3) antagonist SR142801, but not affected by the NK(3) agonist senktide or neurokinin B. The cholinergic contractions to EFS in the small intestine were not affected by SR142801, but dose-dependently inhibited by senktide and neurokinin B. This inhibitory effect was prevented by SR142801 but not by hexamethonium. SR142801, senktide or neurokinin B did not induce any response per se in the stomach and small intestine and did not affect contractions to carbachol.


CONCLUSIONS
NK(3) receptors modulate cholinergic neurotransmission differently in the mouse stomach and small intestine. Blockade of NK(3) receptors enhanced cholinergic transmission in the stomach but not in the intestine. Activation of NK(3) receptors inhibited cholinergic transmission in the small intestine but not in the stomach. This indicates a physiological role for NK(3) receptors in mouse stomach contractility and a pathophysiological role in mouse intestinal contractility.
De Man
J G
JG
Faculty of Medicine, Laboratory of Experimental Medicine and Paediatrics, Division of Gastroenterology, University of Antwerp, Universiteitsplein 1, Antwerp, Belgium. joris.deman@ua.ac.be
De Winter
B Y
BY
De Schepper
H U
HU
Herman
A G
AG
Pelckmans
P A
PA
D000818:Animals; D007082:Ileum / Q000187:drug effects / Q000294:innervation* / Q000502:physiology; D066298:In Vitro Techniques; D051379:Mice; D009119:Muscle Contraction; D010880:Piperidines / Q000494:pharmacology; D011950:Receptors, Cholinergic / Q000502:physiology*; D018039:Receptors, Tachykinin / Q000502:physiology*; D013270:Stomach / Q000187:drug effects / Q000294:innervation* / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*
D010880:Piperidines; D011950:Receptors, Cholinergic; D018039:Receptors, Tachykinin; C091554:SR 142801