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

Abstract

Background and purpose: 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. Experimental approach: 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. 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 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 and implications: 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.