Holzer P, Lippe I T, Heinemann A, Barthó L
Department of Experimental and Clinical Pharmacology, University of Graz, Austria.
Neuropharmacology. 1998;37(1):131-8. doi: 10.1016/s0028-3908(97)00195-0.
The tachykinins substance P and neurokinin A are excitatory cotransmitters of cholinergic enteric neurons, their actions being mediated by NK1, NK2 and NK3 receptors. This study examined which of these receptors are part of the neural circuitry of peristalsis. Peristaltic propulsion in luminally perfused segments of the guinea-pig isolated ileum was elicited by a rise of the intraluminal pressure. The pressure threshold at which peristaltic contractions were triggered was used to quantify drug effects on peristalsis, inhibition of peristalsis being reflected by an increase in the pressure threshold. The NK1, NK2 and NK3 receptor antagonists SR-140333, SR-48968 and SR-142 801 (each at 0.1 microM), respectively, had little effect on peristaltic activity as long as cholinergic transmission was left intact. However, both the NK1 and NK2 receptor antagonist (each at 0.1 microM) abolished peristalsis after cholinergic transmission via muscarinic receptors had been blocked by atropine (1 microM) and peristalsis rescued by naloxone (0.5 microM). When cholinergic transmission via nicotinic receptors was suppressed by hexamethonium (100 microM) and peristalsis restored by naloxone (0.5 microM), only the NK2 receptor antagonist (0.1 microM) was able to attenuate peristaltic performance as deduced from a rise of the peristaltic pressure threshold by 106%. The NK3 receptor antagonist (0.1 microM) lacked a major influence on peristalsis under any experimental condition. It is concluded that tachykinins acting via NK1 and NK2 receptors sustain intestinal peristalsis when cholinergic neuroneuronal and neuromuscular transmission via muscarinic receptors has been suppressed. NK2 receptors help maintaining peristalsis once cholinergic neuroneuronal transmission via nicotinic receptors has been blocked, whereas NK3 receptors play little role in the neural pathways of peristalsis.
速激肽P物质和神经激肽A是胆碱能肠神经元的兴奋性共递质，它们的作用由NK1、NK2和NK3受体介导。本研究检测了这些受体中哪些是蠕动神经回路的一部分。通过腔内压力升高引发豚鼠离体回肠腔内灌注段的蠕动推进。触发蠕动收缩的压力阈值用于量化药物对蠕动的影响，蠕动的抑制通过压力阈值的升高来反映。NK1、NK2和NK3受体拮抗剂SR-140333、SR-48968和SR-142801（各为0.1微摩尔），只要胆碱能传递保持完整，对蠕动活动几乎没有影响。然而，在毒蕈碱受体介导的胆碱能传递被阿托品（1微摩尔）阻断且蠕动被纳洛酮（0.5微摩尔）恢复后，NK1和NK2受体拮抗剂（各为0.1微摩尔）均消除了蠕动。当烟碱受体介导的胆碱能传递被六甲铵（100微摩尔）抑制且蠕动被纳洛酮（0.5微摩尔）恢复时，仅NK2受体拮抗剂（0.1微摩尔）能够减弱蠕动性能，从蠕动压力阈值升高106%可推断出这一点。在任何实验条件下，NK3受体拮抗剂（0.1微摩尔）对蠕动均无主要影响。结论是，当毒蕈碱受体介导的胆碱能神经元间和神经肌肉传递被抑制时，通过NK1和NK2受体起作用的速激肽维持肠道蠕动。一旦烟碱受体介导的胆碱能神经元间传递被阻断，NK2受体有助于维持蠕动，而NK3受体在蠕动的神经通路中作用很小。
