Descending inhibitory reflexes involve P2X receptor-mediated transmission from interneurons to motor neurons in guinea-pig ileum

1. The role of P2X receptors in descending inhibitory reflexes evoked by distension or mucosal distortion in the guinea-pig ileum was studied using intracellular recording from the circular muscle in a two-chambered organ bath. This allowed separate superfusion of the sites of reflex stimulation and recording, thereby allowing drugs to be selectively applied to different parts of the reflex pathway 2. Inhibitory junction potentials (IJPs) evoked by electrical field stimulation (EFS) in the recording chamber were compared with those evoked during reflexes to control for effects of P2 receptor antagonists on neuromuscular transmission. 3. The P2 receptor antagonists suramin (100 muM) and pyridoxal phosphate-6-azophenyl-2',4'-disulphonic acid (10 and 60 muM; PPADS), when added to the recording chamber, depressed reflexly evoked IJPs significantly more than those evoked by EFS. In particular, 10 muM PPADS depressed IJPs evoked by distension or mucosal distortion by about 50%, but had little effect on IJPs evoked by EFS. 4. Blockade of synaptic transmission in the stimulation chamber with a low Ca2+-high Mg2+ solution depressed, but did not abolish, IJPs evoked by distension. The residual reflex IJPs were unaffected by PPADS (10 muM), hyoscine (1 muM), hyoscine plus hexamethonium (200 muM), or hysocine plus hexamethonium plus PPADS in the recording chamber. 5. We conclude that P2X receptors are important for synaptic transmission from descending interneurons to inhibitory motor neurons in descending inhibitory reflex pathways of guinea-pig ileum. Transmission from anally directed axons of distension-sensitive intrinsic sensory neurons to inhibitory motor neurons is unlikely to involve P2X, muscarinic or nicotinic receptors.