Differential role of tachykinin NK3 receptors on cholinergic excitatory neurotransmission in the mouse stomach and small intestine

Background and purpose: Tachykinin NK3 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 NK3 receptors in cholinergic neurotransmission in the mouse...

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Bibliographic Details
Published in:British journal of pharmacology 2008-12, Vol.155 (8), p.1195-1203
Main Authors: De Man, J G, De Winter, B Y, De Schepper, H U, Herman, A G, Pelckmans, P A
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
cholinergic nerves
enteric nervous system
ileum
Ileum - drug effects
Ileum - innervation
Ileum - physiology
In Vitro Techniques
Medical sciences
Mice
Muscle Contraction
neurokinin B
NK3 receptors
Pharmacology. Drug treatments
Piperidines - pharmacology
Receptors, Cholinergic - physiology
Receptors, Tachykinin - physiology
Research Papers
senktide
SR142801
Stomach - drug effects
Stomach - innervation
Stomach - physiology
Synaptic Transmission - physiology
tachykinin
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Summary:Background and purpose: Tachykinin NK3 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 NK3 receptors in cholinergic neurotransmission in the mouse stomach and small intestine. Experimental approach: Muscle strips of the mouse gastric fundus and ileum were mounted in organ baths for tension recordings. Effects of NK3 agonists and antagonists were studied on contractions to EFS of enteric nerves and to carbachol. Key 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 NK3 antagonist SR142801, but not affected by the NK3 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 and implications: NK3 receptors modulate cholinergic neurotransmission differently in the mouse stomach and small intestine. Blockade of NK3 receptors enhanced cholinergic transmission in the stomach but not in the intestine. Activation of NK3 receptors inhibited cholinergic transmission in the small intestine but not in the stomach. This indicates a physiological role for NK3 receptors in mouse stomach contractility and a pathophysiological role in mouse intestinal contractility. British Journal of Pharmacology (2008) 155, 1195–1203; doi:10.1038/bjp.2008.357; published online 22 September 2008
ISSN:0007-1188
1476-5381
DOI:10.1038/bjp.2008.357