Analysis of contributions of acetylcholine and tachykinins to neuro‐neuronal transmission in motility reflexes in the guinea‐pig ileum

Abstract

1 The roles of acetylcholine (ACh) and tachykinins in neuro-neuronal transmission during ascending excitatory and descending inhibitory reflexes were studied by recording intracellular reflex responses of the circular muscle to physiological stimuli. Experiments were carried out in opened segments of guineapig ileum in an organ bath that was partitioned so that three regions could be independently exposed to drugs. 2 Ascending excitatory reflexes evoked by either distension from the serosal side or compression of the mucosa were depressed by 55% and 85%, respectively, in the presence of hexamethonium (200 gM) and by 30% and 45%, respectively, by a desensitizing concentration of the selective NK3 receptor agonist, senktide (1 gM), in the chamber in which reflexes were initiated. Together, hexamethonium and senktide abolished reponses to compression. A residual response to distension persisted. This was abolished by hyoscine (1 uM).3 Hexamethonium (200 gM) abolished ascending reflexes when applied to the region between the stimulus and the recording sites, or to the recording chamber. 4 Descending reflex responses were reduced by 35% by synaptic blockade in the stimulus chamber with physiological saline containing 0.1 mM Ca2" plus 10 mM Mg2'. Senktide (1 gM) in the stimulus chamber reduced distension reflexes to the same extent as synaptic blockade, whereas hexamethonium (200 gM) and hyoscine (1 gM) depressed responses by less than 20%. Responses to compression were reduced by 40% by senktide alone, while senktide and hexamethonium together reduced responses by 60%, an effect similar to synaptic blockade. Under these conditions, hyoscine in the stimulus chamber restored reflexes evoked by distension, but did not alter those evoked by mucosal compression. 5 Total synaptic blockade in the intermediate chamber, between stimulus and recording sites, reduced descending reflex responses by more than 90%. In contrast, hexamethonium (200 gM) had no effect and hyoscine (1 gM) reduced only the responses to distension (by 30%). Senktide (1 gM) depressed responses to both stimuli by approximately 80%.6 Application of hexamethonium (200 gM) to the recording chamber depressed descending reflex responses to distension applied in the near stimulation chamber by 15%, but had no effect on responses to compression in the near chamber or to either stimulus applied in the far chamber. 7 Descending reflexes evoked by near chamber stimuli were unaffected by hyoscine (1 gM) or senktide (1 gM) applied to the recording chamber; hyoscine enhanced reflexes evoked by compression in the far chamber by 50%. 8 For the ascending excitatory reflex pathway, it is concluded that transmission from sensory neurones is mediated by ACh acting via both nicotinic and muscarinic receptors, and by tachykinins acting at NK3 receptors. Transmission from ascending interneurones appears to be predominantly via nicotinic receptors. The descending inhibitory pathways are more complex, and while transmission from sensory neurones involves nicotinic, muscarinic ...

Regulation of Guinea pig intestinal peristalsis by endogenous endothelin acting at ETB receptors

“…These drugs were used because nicotinic acetylcholine receptors mediate excitatory transmission within the enteric nerve plexuses and the excitatory motor neurons of the gut transmit via acetylcholine acting on muscarinic receptors and substance P/neurokinin A acting on NK 1 and NK 2 receptors. 26,29,30 SR-140,333 and SR-144,190 were used at concentrations known to be effective and selective for NK 1 and NK 2 receptors, respectively, but devoid of any major influence on peristalsis on their own. 26,31 Atropine and hexamethonium, in contrast, caused a temporary peristaltic arrest which, as previously observed, [32][33][34] was released after some time, enabling us to test drug effects on noncholinergic propulsive motility.…”

“…The inability of atropine, SR-140,333, and SR-144,190 to prevent the properistaltic action of ET-1 does not rule out any implication of excitatory motor neurons releasing acetylcholine, substance P, and neurokinin A, given that these transmitters synergize in neuromuscular transmission. 26,29,30,33,34 The antiperistaltic action of STX-6c was analyzed with respect to the possibility that this ET B receptor agonist depresses peristalsis via activation of inhibitory motor neurons, which in the guinea pig intestine relax the muscle primarily via release of NO, ATP, vasoactive intestinal polypeptide, and/or pituitary adenylate cyclaseactivating peptide. [35][36][37][38] However, peristaltic motor inhibition caused by STX-6c remained unaltered by an effective concentration (300 µmol/L) of the NO synthase inhibitor L-NAME, 25,39 which is in line with a lack of NO involvement in ET-induced suppression of intestinal muscle contractility.…”

Interactions of Serotoninergic, Cholinergic, and Tachykinin‐Containing Nerve Elements in the Rabbit Small Intestine

“…last but not least, orally and anally directed interneurons (Ekblad et al, 1987;Brookes et al, 1991Brookes et al, , 1992Brookes et al, , 1997Johnson et al, 1996Johnson et al, , 1998. Tachykinins utilized as transmitters from enteric neurons target numerous enteric elements through NK1, NK2, or NK3 receptors.…”

“…Tachykinins utilized as transmitters from enteric neurons target numerous enteric elements through NK1, NK2, or NK3 receptors. NK2 receptors occur primarily on muscle, whereas NK3 receptors are involved in neuroneuronal transmission (Johnson et al, 1996(Johnson et al, , 1998Portbury et al, 1996a;Jenkinson et al, 1999Jenkinson et al, , 2000Lecci et al, 2002). NK1 receptors have been shown acting on both muscle and enteric neurons.…”

Purinergic mechanisms in the control of gastrointestinal motility

“…This problem has been similar for many other compounds found to act as either neurotransmitters or modulators within the intestine. For example, although tachykinin-mediated slow EPSPs are prominent in many enteric neurons [61,62] and simple motility reflexes are altered by specific tachykinin antagonists [185,186], it has been very difficult to show a role for neural tachykinin receptors in normal motility patterns. It seems likely that many of the effects of these relatively enigmatic transmitters and modulators will be seen only in pathological circumstances, as with the A 1 receptor involvement in the postoperative ileus.…”