Roles of neuronal NK₁ and NK₃ receptors in synaptic transmission during motility reflexes in the guinea‐pig ileum

Abstract

The role of NK1 and NK3 receptors in synaptic transmission between myenteric neurons during motility reflexes in the guinea‐pig ileum was investigated by recording intracellularly the reflex responses of the circular muscle to distension or compression of the mucosal villi. Experiments were performed in a three‐chambered organ bath that enabled drugs to be selectively applied to different sites along the reflex pathways. When applied in the recording chamber, an NK1 receptor antagonist, SR140333 (100 nm), reduced by 40–50% the amplitudes of inhibitory junction potentials (i.j.ps) evoked in the circular muscle by activation of descending reflex pathways. This effect was abolished when synaptic transmission in the stimulus region was blocked with physiological saline containing 0.1 mm Ca2+ plus 10 mm Mg2+, leaving only the component of the descending reflex pathway conducted via long anally directed collaterals of intrinsic sensory neurons. SR140333 (100 nm) had no effect on descending reflex i.j.ps when applied to the stimulus region. Ascending reflexes were also unaffected by SR140333 in the stimulus region or between the stimulus and recording sites. Septide (10 nm), an NK1 receptor agonist, enhanced descending reflexes by 30–60% when in the recording chamber. [Sar9,Met(O2)11]substance P had no effect at 10 nm, but potentiated distension‐evoked reflexes at 100 nm. A selective NK3 receptor antagonist, SR142801 (100 nm), when applied to the stimulus region, reduced the amplitude of descending reflex responses to compression by 40%, but had no effect on responses to distension. SR142801 (100 nm) had no effect when applied to other regions of the descending reflex pathways. SR142801 (100 nm) only inhibited ascending reflexes when applied at the recording site. However, after nicotinic transmission in the stimulus region was blocked, SR142801 (100 nm) at this site reduced responses to compression. Contractions of the circular muscle of isolated rings of ileum evoked by low concentrations of septide, but not [Sar9,Met(O2)11]substance P, were potentiated by tetrodotoxin (300 nm). Contractile responses evoked by an NK3 receptor agonist, senktide, were non‐competitively inhibited by SR142801. After excitatory neuromuscular transmission was blocked, senktide produced inhibitory responses that were also antagonised by SR142801, but to a lesser extent and in an apparently competitive manner. These results indicate that tachykinins acting via NK1 receptors partly mediate transmission to inhibitory motor neurons. NK3 receptors play a role in transmission from intrinsic sensory neurons and from ascending interneurons to excitatory motor neurons during motility reflexes. British Journal of Pharmacology (1998) 124, 1375–1384; doi:

Synaptic Transmission at Functionally Identified Synapses in the Enteric Nervous System: Roles for Both Ionotropic and Metabotropic Receptors

“…Transmission between ascending interneurons is mediated via nAChRs and between ascending interneurons and excitatory motor neurons (EMNs) is via nAChRs and NK 3 receptors. tive to intestinal distension (probably myenteric AH/Dogiel type II neurons) to ascending interneurons appears to be mediated by ACh acting at nAChR, by ACh acting at muscarinic receptors and by a tachykinin acting at NK 3 receptors [55,126]. It is only abolished when all three receptor subtypes are blocked.…”

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.…”

“…NK1 receptors have been shown acting on both muscle and enteric neurons. More precisely, functional classes of neurons that expressed NK1 receptors were NOS-IR inhibitory motorneurons, ACh/SP-IR excitatory motorneurons, secretomotor neurons, and ChAT/calbindin-IR sensory neurons (Portbury et al, 1996b;Johnson et al, 1998;Lomax et al, 1998;Lecci et al, 2002;Thornton and Bornstein, 2002).…”

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.…”