Search PubMed⌕ Search

Biomedical subjects

J B Furness

Publications and source records attributed to J B Furness.

At least 37 records · Page 2Linked to original sources
PubMed2001

Gene expression and localization of GABA(C) receptors in neurons of the rat gastrointestinal tract.

The effects of GABA in the CNS are mediated by three different GABA receptors: GABA(A), GABA(B) and GABA(C) receptors. GABA(A) and GABA(B) receptors, but not yet GABA(C) receptors, have been demonstrated in the enteric nervous system, where GABA has been proposed to be a transmitter. The purpose of this study was to determine whether GABA(C) receptors are present and thus may play a role in mediating the effects of GABA in the myenteric plexus of the rat gastrointestinal tract. We examined the expression of the three known GABA(C) receptor subunits, rho1, rho2 and rho3, in the rat duodenum, ileum and colon using the reverse transcriptase-polymerase chain reaction. We determined the localization of GABA(C) receptors in the myenteric plexus of these regions using two different antisera directed against GABA(C) receptor subunits. The polymerase chain reaction revealed that all three subunits were expressed in the gastrointestinal tract. When the layers of the intestine were separated and the layer containing myenteric neurons was assayed, the rho3 subunit was found in the ileum and colon, whereas rho1 was expressed in the duodenum and weakly in the colon and rho2 was expressed in the ileum. Immunocytochemistry revealed numerous labeled neurons in the myenteric plexus of each region. Colocalization showed that a large proportion of calbindin plus calretinin immunoreactive neurons (intrinsic primary afferent neurons) were immunoreactive for the GABA(C) receptor, and that 56% of nitric oxide synthase immunoreactive neurons (inhibitory motor neurons) exhibited the receptor. These results indicate that GABA(C) receptors of differing subunit compositions are expressed by neurons in the rat gastrointestinal tract. The effects of GABA on intrinsic sensory and on inhibitory motor neurons are likely to be mediated in part through GABA(C) receptors.

Animals↗
PubMed2001

The relationship between propagated contractions and pseudoaffective changes in blood pressure in response to intestinal distension.

We investigated the relationship between changes in small intestinal motility and changes in blood pressure and heart rate in response to intestinal distension. Rats were maintained under stable anaesthesia with alpha-chloralose, and jejunal motility, blood pressure and heart rate were recorded. Pressure changes during propagated contractions of the circular muscle were recorded in the jejunum when the intraluminal pressure was maintained at 10 mmHg. Raising the pressure in 10 mmHg increments from 10 mmHg to 40 mmHg increased the frequency of propagated contractions from 0.30 +/- 0.06 min-1 (mean +/- SEM) to 1.29 +/- 0.09 per min. In contrast, amplitudes of contractions above baseline pressure decreased from 19.5 +/- 0.6 mmHg to 7.8 +/- 0.5 mmHg. Simultaneously, blood pressure and heart rate were both increased. Pretreatment of rats with capsaicin, or severing the mesenteric nerves acutely, prevented these cardiovascular responses, but did not influence the changes in propagated activity caused by distension. Propagated contractions were blocked by hexamethonium (10 mg kg-1, intravenously [i.v.]) and by local application of 2% lidocaine, but propulsion was unchanged by hyoscine (1 mg kg-1, i.v.). Phentolamine (1 mg kg-1, i.v.) increased the frequency of propagated contractions. The methods described in this work allow the effects of drugs on intrinsic intestinal reflexes to be distinguished from their effects on extra-intestinal, pseudoaffective reflexes. In addition, unlike other experiments using anaesthetized rats, blood pressure increased in response to distension, as it does in mammals that are not anaesthetized. The experiments demonstrate that the neural pathways for propagated contractions that rely on intrinsic nerve circuits, including intrinsic primary afferent neurones, and the neural pathways for extrinsic reflexes that signal pain or discomfort in the intestine, which involve capsaicin-sensitive spinal afferent neurones, are independent.

Adrenergic alpha-Antagonists↗
PubMed2001

Immunohistochemical demonstration of the NK(1) tachykinin receptor on muscle and epithelia in guinea pig intestine.

BACKGROUND AND AIMS: Previous immunohistochemical studies failed to reveal neurokinin (NK)(1) tachykinin receptors on intestinal muscle, despite convincing pharmacologic data indicating their presence. This study aimed to apply optimal immunohistochemical methods to reveal the receptors. METHODS: NK(1)-receptor immunoreactivity was examined by confocal microscopy in tissue incubated with or without 10(-7) mol/L substance P (SP), 10(-7) mol/L SP plus 10(-6) mol/L NK(1) receptor antagonist (CP99994), or with fluorescent cyanine 3.18 (Cy3) SP. RESULTS: Without incubation, NK(1)-receptor immunoreactivity was strong on muscle of the rectum and distal colon and weak in proximal colon and small intestine. NK(1) receptor was located on the surface of muscle cells in all gut regions. Exposure to SP increased the intensity of immunoreactivity, and the receptor moved into the cytoplasm. Mobilization of the receptor by SP was blocked by the NK(1)-receptor antagonist CP99994. Cy3-SP was internalized by muscle cells and colocalized with the receptor. NK(1)-receptor immunoreactivity occurred on crypt epithelial cells in the small intestine and the base of glands in the proximal colon. CONCLUSIONS: The NK(1) receptor occurs on the external muscle throughout the small and large intestines. SP binds and triggers NK(1)-receptor aggregation and internalization in the muscle.

Animals↗
PubMed2001

Afterhyperpolarization current in myenteric neurons of the guinea pig duodenum.

Whole cell patch and cell-attached recordings were obtained from neurons in intact ganglia of the myenteric plexus of the guinea pig duodenum. Two classes of neuron were identified electrophysiologically: phasically firing AH neurons that had a pronounced slow afterhyperpolarization (AHP) and tonically firing S neurons that lacked a slow AHP. We investigated the properties of the slow AHP and the underlying current (I(AHP)) to address the roles of Ca(2+) entry and Ca(2+) release in the AHP and the characteristics of the K(+) channels that are activated. AH neurons had a resting potential of -54 mV and the AHP, which followed a volley of three suprathreshold depolarizing current pulses delivered at 50 Hz through the pipette, averaged 11 mV at its peak, which occurred 0.5-1 s following the stimulus. The duration of these AHPs averaged 7 s. Under voltage-clamp conditions, I(AHP)'s were recorded at holding potentials of -50 to -65 mV, following brief depolarization of AH neurons (20-100 ms) to positive potentials (+35 to +50 mV). The null potential of the I(AHP) at its peak was -89 mV. The AHP and I(AHP) were largely blocked by omega-conotoxin GVIA (0.6-1 microM). Both events were markedly decreased by caffeine (2-5 mM) and by ryanodine (10-20 microM) added to the bathing solution. Pharmacological suppression of the I(AHP) with TEA (20 mM) or charybdotoxin (50-100 nM) unmasked an early transient inward current at -55 mV following step depolarization that reversed at -34 mV and was inhibited by niflumic acid (50-100 microM). Mean-variance analysis performed on the decay of the I(AHP) revealed that the AHP K(+) channels have a mean chord conductance of ~10 pS, and there are ~4,000 per AH neuron. Spectral analysis showed that the AHP channels have a mean open dwell time of 2.8 ms. Cell-attached patch recordings from AH neurons confirmed that the channels that open following action currents have a small unitary conductance (10-17 pS) and open with a high probability (</=0.5) within the first 2 s following an action potential. These results indicate that the AHP is largely a consequence of Ca(2+) entry through omega-conotoxin GVIA-sensitive Ca(2+) channels during the action potential, Ca(2+)-triggered Ca(2+) release from caffeine-sensitive stores and the opening of Ca(2+)-sensitive small-conductance K(+) channels.

Action Potentials↗
PubMed2001

Locations and innervation of cell bodies of sympathetic neurons projecting to the gastrointestinal tract in the rat.

The locations of cell bodies of sympathetic neurons projecting to the stomach, the duodenum, the ileum, the colon, the spleen and the pancreas have been studied using retrograde tracing. Projections arose from both pre- and paravertebral ganglia. In the rat, the prevertebral ganglia are the paired coeliac ganglia lying caudo-lateral to the root of the coeliac artery, paired splanchnic ganglia in the abdominal segments of the greater splanchnic nerves, unpaired superior mesenteric and inter-renal ganglia and the inferior mesenteric ganglia. The projections from the prevertebral sympathetic ganglia to the different parts of the gut were organised somatotopically. The most rostral ganglia (splanchnic, coeliac, and superior mesenteric ganglia) contained neurons innervating all regions of the gastrointestinal tract, the pancreas and the spleen. The inter-renal and inferior mesenteric ganglia, located more caudally, contained neurons innervating the distal part of the gut (distal ileum and colon). The innervation of the spleen and the pancreas came from the closest ganglia (sympathetic chains, splanchnic and coeliac ganglia). This organotopic organisation was not found in the sympathetic chain ganglia; the innervation of all organs came predominantly from the lower part of the thoracic chains. A large proportion of the retrogradely labelled nerve cells in the splanchnic ganglia received nitric oxide synthase immunoreactive innervation probably from the spinal cord. In the other prevertebral ganglia, most of the neurons received nitric oxide synthase immunoreactive innervation and/or bombesin immunoreactive innervation. This leads to the conclusion that, in these ganglia, many neurons receive projections from the gastrointestinal tract in addition to the spinal cord.

Animals↗
PubMed2001

TAK-637. Takeda.

Abbott and Takeda are developing TAK-637, an orally active NK1 antagonist, for the potential treatment of urinary incontinence, depression, irritable bowel syndrome and pollakiuria. By November 1999, it was in phase II trials in Europe and phase I in Japan and the US for urinary incontinence [348496], [350686]. By October 2000, phase II trials had been initiated in the US for urinary incontinence, depression and IBS [381167], [386950], [419868], and in May 2001, these were scheduled to finish in 2002 [412024].

Animals↗
PubMed2000

Identification of intestinofugal neurons projecting to the coeliac and superior mesenteric ganglia in the rat.

Intestinofugal neurons are parts of the afferent limbs of inhibitory intestino-intestinal reflexes. These neurons have been mapped in guinea-pigs, where they have a gradient of increasing frequency of occurrence from oral to anal, but not in other species. In the present work in the rat, a species that is more amenable to physiological study than the guinea-pig, we have used retrograde tracing to map the distribution of the cell bodies of intestinofugal neurons projecting to the coeliac-superior mesenteric ganglion complex. Labelled nerve cells were found in the myenteric, but not the submucosal plexus. They were mono-axonal neurons, most with Dogiel type I morphology, and were immunoreactive for choline acetyltransferase, implying that they are cholinergic, which is consistent with functional studies. The cells increased in number per unit area from the stomach, through the small intestine, to the caecum. The results are consistent with physiological studies that reveal distal to proximal inhibitory reflexes that are more potent from distal compared to proximal sites.

Afferent Pathways↗
PubMed2000

The soma and neurites of primary afferent neurons in the guinea-pig intestine respond differentially to deformation.

1. Intrinsic primary afferent neurons in the small intestine are exposed to distortion of their processes and of their cell bodies. Recordings of mechanosensitivity have previously been made from these neurons using intracellular microelectrodes, but this form of recording has not permitted detection of generator potentials from the processes, or of responses to cell body distortion. 2. We have developed a technique to record from enteric neurons in situ using patch electrodes. The mechanical stability of the patch recordings has allowed recording in cell-attached and whole cell configuration during imposed movement of the neurons. 3. Pressing with a fine probe initiated generator potentials (14 +/- 9 mV) from circumscribed regions of the neuron processes within the same myenteric ganglion, at distances from 100 to 500 microm from the cell body that was patched. Generator potentials persisted when synaptic transmission was blocked with high Mg2+, low Ca2+ solution. 4. Soma distortion, by pressing down with the whole cell recording electrode, inhibited action potential firing. Consistent with this, moderate intra-electrode pressure (10 mbar; 1 kPa) increased the opening probability of large-conductance (BK) potassium channels, recorded in cell-attached mode, but suction was not effective. In outside-out patches, suction, but not pressure, increased channel opening probability. Mechanosensitive BK channels have not been identified on other neurons. 5. The BK channels had conductances of 195 +/- 25 pS. Open probability was increased by depolarization, with a half-maximum activation at a patch potential of 20 mV and a slope factor of 10 mV. Channel activity was blocked by charybdotoxin (20 nM). 6. Stretch that increased membrane area under the electrode by 15 % was sufficient to double open probability. Similar changes in membrane area occur when the intestine changes diameter and wall tension under physiological conditions. Thus, the intestinal intrinsic primary afferent neurons are detectors of neurite distortion and of compression of the soma, these stimuli having opposite effects on neuron excitability.

Action Potentials↗
PubMed2000

Types of neurons in the enteric nervous system.

This paper, written for the symposium in honour of more than 40 years' contribution to autonomic research by Professor Geoffrey Burnstock, highlights the progress made in understanding the organisation of the enteric nervous system over this time. Forty years ago, the prevailing view was that the neurons within the gut wall were post-ganglionic neurons of parasympathetic pathways. This view was replaced as evidence accrued that the neurons are part of the enteric nervous system and are involved in reflex and integrative activities that can occur even in the absence of neuronal influence from extrinsic sources. Work in Burnstock's laboratory led to the discovery of intrinsic inhibitory neurons with then novel pharmacology of transmission, and precipitated investigation of neuron types in the enteric nervous system. All the types of neurons in the enteric nervous system of the small intestine of the guinea-pig have now been identified in terms of their morphologies, projections, primary neurotransmitters and physiological identification. In this region there are 14 functionally defined neuron types, each with a characteristic combination of morphological, neurochemical and biophysical properties. The nerve circuits underlying effects on motility, blood flow and secretion that are mediated through the enteric nervous system are constructed from these neurons. The circuits for simple motility reflexes are now known, and progress has been made in analysing those involved in local control of blood flow and transmucosal fluid movement in the small intestine.

Animals↗
PubMed2000

Origins of cholinergic inputs to the cell bodies of intestinofugal neurons in the guinea pig distal colon.

Integration of function between gut regions is mediated by means of hormones and long neuronal reflex pathways. Intestinofugal neurons, which participate in one of these pathways, have cell bodies within the myenteric plexus and project their axons from the gut with the mesenteric nerves. They form excitatory synapses on neurons in prevertebral ganglia that in turn innervate other gut regions. The aim of the present study was to characterise immunohistochemically the synaptic input to intestinofugal neurons. The cell bodies of intestinofugal neurons that project from the distal colon were labelled with Fast Blue that was injected into the inferior mesenteric ganglia. Varicosities surrounding Fast Blue-labelled neurons were analysed for immunoreactivity for the vesicular acetylcholine transporter, vasoactive intestinal peptide, and bombesin. Most intestinofugal neurons were surrounded by nerve terminals immunoreactive for the vesicular acetylcholine transporter; many of these terminals also contained vasoactive intestinal peptide and bombesin immunoreactivity. This combination of markers occurs in axons of descending interneurons. Extrinsic denervation had no effect on the distribution of cholinergic terminals around intestinofugal neurons. A decrease in the number of vesicular acetylcholine transporter and vasoactive intestinal peptide immunoreactive terminals occurred around nerve cells immediately anal, but not oral, to myotomy operations. Consistent with previous physiological studies, it is concluded that intestinofugal neurons receive cholinergic synaptic input from other myenteric neurons, including cholinergic descending interneurons. Thus, intestinofugal neurons are second, or higher, order neurons in reflex pathways, although physiological data indicate that they also respond directly to distension of the gut wall.

Afferent Pathways↗
PubMed2000

Shapes and projections of tertiary plexus neurons of the guinea-pig small intestine.

The axons of neurons that innervate the longitudinal muscle of the small intestine in small mammals such as rabbit, rat, guinea pig and mouse form a network, the tertiary plexus, against the inner surface of the muscle. In general, because of their substantial overlap, it has not been possible to follow the ramifications of individual axons in the tertiary plexus. In the present work, the longitudinal muscle motor neurons were filled with marker dyes through an intracellular microelectrode, and their morphologies and projections were examined in whole-mount preparations of longitudinal muscle and myenteric plexus. Most neurons that were examined were in the small intestine (ileum and duodenum), but a few were examined in the distal colon. Neurons in all regions had similar morphologies and projections. The cell bodies were amongst the smallest in myenteric ganglia, with major and minor axes of 14 microns and 25 microns (mean, n = 40) in the plane of the myenteric plexus. Each neuron had a single axon that branched extensively in the tertiary plexus, most had multiple lamellar dendrites and a few had filamentous dendrites or a mixture of filamentous and lamellar dendrites. The mean area of muscle covered by an axon and its branches extended 1.6 mm orally to anally and 1.7 mm circumferentially. The area covered was 2.8 +/- 1.9 mm2 (mean +/- SD, n = 23). From the density of occurrence of cell bodies, it can be calculated that each point in the longitudinal muscle is innervated by the processes of about 100 motor neurons and is influenced by electrotonic conduction of signals through the muscle by about 300 motor neurons.

Animals↗
PubMed2000

Neurochemical classification of enteric neurons in the guinea-pig distal colon.

Previous studies have identified the chemistries, shapes, projections and electrophysiological characteristics of several populations of neurons in the distal colon of the guinea-pig but it is unknown how these characteristics correlate to define the classes of neurons present. We have used double-label immunohistochemical techniques to identify neurochemically distinct subgroups of enteric neurons in this region. On the basis of colocalisation of neurochemical markers and knowledge gained from previous studies of neural projections, 17 classes of neurons were identified. The myenteric plexus contained the cell bodies of 13 distinct types of neurons. Four classes of descending interneurons and three classes of ascending interneurons were identified, together with inhibitory and excitatory motor neurons to both the circular and longitudinal muscle layers. Dogiel type II neurons, which are presumed to be intrinsic primary afferent neurons, were located in myenteric and submucosal ganglia; they were all immunoreactive for choline acetyltransferase and often calbindin and tachykinins. Three classes of secretomotor neurons with cell bodies in submucosal ganglia were defined. Two of these classes were immunoreactive for choline acetyltransferase and the other class was immunoreactive for both vasoactive intestinal peptide and nitric oxide synthase. Some of the secretomotor neurons probably also have a vasomotor function. The neural subtypes defined in the present study are similar in many respects to those found in the small intestine, although differences are evident, especially in populations of interneurons. These differences presumably reflect the differing physiological roles of the two intestinal regions.

Animals↗
PubMed2000

Inputs from intrinsic primary afferent neurons to nitric oxide synthase-immunoreactive neurons in the myenteric plexus of guinea pig ileum.

Nitric oxide synthase (NOS) immunoreactivity occurs in two groups of neurons in the guinea pig small intestine: descending interneurons that are also immunoreactive for choline acetyltransferase (ChAT), and inhibitory motor neurons that lack ChAT immunoreactivity. Interneurons that are involved in local reflexes would be expected to have inputs from intrinsic primary afferent (sensory) neurons, most of which are calbindin-immunoreactive. We examined this possibility using triple staining for NOS, ChAT and calbindin immunoreactivity and investigated the relationships between calbindin-immunoreactive varicosities and the cell bodies of NOS-immunoreactive neurons, using high-resolution confocal microscopy and electron microscopy. By confocal microscopy, we found that the cell bodies of ChAT/NOS interneurons received 84 +/- 23 (mean +/- SD) direct appositions from calbindin-immunoreactive varicosities and that the cell bodies of NOS-inhibitory motor neurons received 82 +/- 20 appositions. Electron-microscopic examination of the relations of 265-calbindin-immunoreactive varicosities, at distances within the resolution of the confocal microscope (300 nm), to 30 NOS-immunoreactive nerve cells indicated that 84% formed close contacts or synapses and 16% were separated from neurons by thin glial cell processes. Thus, each NOS-immunoreactive nerve cell receives about 70 synaptic inputs or close contacts from the calbindin-immunoreactive varicosities of intrinsic primary afferent neurons. It is concluded that there are monosynaptic reflex connections in which intrinsic primary afferent neurons synapse directly with motor neurons and di- or poly-synaptic reflexes in which ChAT- and NOS-immunoreactive neurons are interneurons, interposed between intrinsic primary afferent neurons and NOS-inhibitory neurons.

Afferent Pathways↗
PubMed2000

Independent endocytosis of the NK(1) and NK(3) tachykinin receptors in neurons of the rat myenteric plexus.

In the myenteric plexus of rat ileum, NK(1) and NK(3) receptors are co-located almost exclusively on neurons of a single population. This study compares endocytosis of NK(1) and NK(3) receptors in these neurons. In the absence of agonist, 26.2+/-2.8% of NK(1) receptor and 29.1+/-1.1% of NK(3) receptor was located in the cytoplasm of the neurons; the remaining receptor was on the surface. The tachykinin neurotransmitters, substance P (10 pM-10 microM) and neurokinin A (10 pM-100 microM), both induced concentration-dependent endocytosis of NK(1) and NK(3) receptors. The selective NK(1) receptor agonist, [Sar(9),Met(O(2))(11)]-substance P (1 microM), induced endocytosis of NK(1) receptor (64.2+/-1.5% in cytoplasm) but not NK(3) receptor (32.9+/-5.0%). The NK(1) receptor endocytosis was reduced by the selective NK(1) receptor antagonist, CP-99994 (100 nM), but not by the selective NK(3) receptor antagonist, SR-142801 (1 microM). The selective NK(3) receptor agonist, senktide (10 nM), induced endocytosis of NK(3) receptor (61.2+/-5.4%) but not NK(1) receptor (34.0+/-4.5%). The NK(3) receptor endocytosis was blocked by SR-142801 but not by CP-99994. We also investigated the effects of monensin, which generally blocks recycling of endocytosed receptor. In the absence or presence of exogenous agonist, monensin caused a build-up of NK(1) receptor, but not NK(3) receptor, in the cytoplasm of neurons.The results demonstrate independent, agonist-induced endocytosis of NK(1) and NK(3) receptors in neurons of the myenteric plexus of rat ileum and suggest that the mechanisms of recycling of NK(1) and NK(3) receptors differ.

Animals↗
PubMed2000

The terminals of myenteric intrinsic primary afferent neurons of the guinea-pig ileum are excited by 5-hydroxytryptamine acting at 5-hydroxytryptamine-3 receptors.

The aim of this study was to identify the receptor type(s) by which 5-hydroxytryptamine applied to the intestinal mucosa excites the terminals of myenteric AH neurons. The AH neurons have been identified as the intrinsic primary afferent (sensory) neurons in guinea-pig small intestine and 5-hydroxytryptamine has been identified as a possible intermediate in the sensory transduction process. Intracellular recordings were taken from AH neurons located within 1mm of intact mucosa to which 5-hydroxytryptamine was applied. Trains of action potentials and/or slow depolarizing responses were recorded in AH neurons in response to mucosal application of 5-hydroxytryptamine (10 or 20microM) or the 5-hydroxytryptamine-3 receptor agonist, 2-methyl-5-hydroxytryptamine (1 or 3mM), and to electrical stimulation of the mucosa. The 5-hydroxytryptamine-2 receptor agonist, alpha-methyl-5-hydroxytryptamine (100microM), and the 5-hydroxytryptamine-1,2,4 receptor agonist, 5-methoxytryptamine (10microM), did not elicit such responses. The 5-hydroxytryptamine-3 receptor-selective antagonist, granisetron (typically 1microM), and the 5-hydroxytryptamine-3,4 receptor antagonist, tropisetron (typically 1microM), each reduced or abolished the responses to 5-hydroxytryptamine, while the selective 5-hydroxytryptamine-4 receptor antagonist, SB 204070 (1microM), did not. It is concluded that application of 5-hydroxytryptamine to the mucosa activates a 5-hydroxytryptamine-3 receptor that triggers action potential generation in the mucosal nerve terminals of myenteric AH neurons.

5-Methoxytryptamine↗
PubMed2000

Evidence for functional NK1-tachykinin receptors on motor neurones supplying the circular muscle of guinea-pig small and large intestine.

The guinea-pig intestine was investigated to determine which neurones are excited via NK1 receptors. The specific NK1 receptor agonists [Sar9, Met(O2)11]-SP and septide contracted the circular muscle of all regions via a tetrodotoxin (TTX)-insensitive mechanism. In the proximal colon, they also evoked a TTX-sensitive relaxation; in the distal colon, the contractions were larger when nerve impulses were blocked with TTX, indicating that the agonists excited inhibitory motor neurones. In the duodenum and ileum, TTX reduced agonist-evoked contractions indicating that excitatory motor neurones were activated. In the presence of indomethacin, TTX enhanced contractions of ileal circular muscle evoked by these agonists suggesting that NK1 receptors were on inhibitory motor neurones. Blockade of nitric oxide synthase (NOS) enhanced NK1 receptor agonist evoked contractions of duodenal circular muscle, indicating that the agonists excite inhibitory motor neurones in duodenum. Neurones immunoreactive for NK1 receptors were studied in the duodenum and distal colon. As reported previously for the ileum, 1 some neurones were immunoreactive for NOS and had Dogiel type I morphology; features characteristic of inhibitory motor neurones. In conclusion, there are functional NK1 receptors on excitatory and inhibitory motor neurones in the guinea-pig small intestine and on inhibitory motor neurones in the colon.

Animals↗