TACHYKININ NK1 AND NK2 RECEPTOR-MEDIATED CONTROL OF PERISTALTIC PROPULSION IN THE GUINEA-PIG SMALL-INTESTINE IN-VITRO

The tachykinins substance P and neurokinin A are excitatory cotransmit ters of cholinergic enteric neurons, their actions being mediated by N K1, NK2 and NK3 receptors. This study examined which of these receptor s are part of the neural circuitry of peristalsis. Peristaltic propuls ion in luminally perfused segments of the guinea-pig isolated ileum wa s elicited by a rise of the intraluminal pressure. The pressure thresh old at which peristaltic contractions were triggered was used to quant ify drug effects on peristalsis, inhibition of peristalsis being refle cted by an increase in the pressure threshold. The NK1, NK2 and NK3 re ceptor antagonists SR-140333: SR-48968 and SR-142801 (each at 0.1 mu M ), respectively, had little effect on peristaltic activity as long as cholinergic transmission was left intact. However, both the NK1 and NK 2 receptor antagonist (each at 0.1 mu M) abolished peristalsis after c holinergic transmission via muscarinic receptors had been blocked by a tropine (1 mu M) and peristalsis rescued by naloxone (0.5 mu M). When cholinergic transmission via nicotinic receptors was suppressed by hex amethonium (100 mu M) and peristalsis restored by naloxone (0.5 mu M), only the NK2 receptor antagonist (0.I mu M) was able to attenuate per istaltic performance as deduced from a rise of the peristaltic pressur e threshold by 106%. The NK3 receptor antagonist (0.1 mu M) lacked a m ajor influence on peristalsis under any experimental condition. It Is concluded that tachykinins acting via NK1 and NK2 receptors sustain in testinal peristalsis when cholinergic neuroneuronal and neuromuscular transmission via muscarinic receptors has been suppressed. NK2 recepto rs help maintaining peristalsis once cholinergic neuroneuronal transmi ssion via nicotinic receptors has been blocked, whereas NK3 receptors play little role in the neural pathways of peristalsis. (C) 1997 Elsev ier Science Ireland Ltd. All rights reserved.