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Slow excitatory synaptic transmission mediated by P2Y1 receptors in the guinea-pig enteric nervous system.

Electrophysiological recording was used to study a type of slow excitatory postsynaptic potential (slow EPSP) that was mediated by release of ATP and its action at P2Y1 receptors on morphologically identified neurones in the submucosal plexus of guinea-pig small intestine. MRS2179, a selective P2Y1 purinergic receptor antagonist, blocked both the slow EPSP and mimicry of the EPSP by exogenously applied ATP. Increased conductance accounted for the depolarization phase of the EPSP, which occurred exclusively in neurones with S-type electrophysiological behaviour and uniaxonal morphology. The purinergic excitatory input to the submucosal neurones came from neighbouring neurones in the same plexus, from neurones in the myenteric plexus and from sympathetic postganglionic neurones. ATP-mediated EPSPs occurred coincident with fast nicotinic synaptic potentials evoked by the myenteric projections and with noradrenergic IPSPs evoked by sympathetic fibres that innervated the same neurones. The P2Y1 receptor on the neurones was identified as a metabotropic receptor linked to activation of phospholipase C, synthesis of inositol 1,4,5-trisphosphate and mobilization of Ca2+ from intracellular stores.

Adenosine Diphosphate↗

Three-dimensional distribution of vasoactive intestinal polypeptide-containing structures in the rat stomach and their origins using whole mount tissue.

The three-dimensional distribution of vasoactive intestinal polypeptide (VIP)-like immunoreactive (VIPLI) structures in rat stomach and their origins were investigated using the indirect immunofluorescence method in whole mounted tissue. The present study demonstrates a very dense VIPLI fiber meshwork in the circular muscle layer, longitudinal muscle layer and myenteric plexus. In the muscle layers VIPLI immunoreactive fibers run parallel to the muscle. VIPLI fibers are distributed evenly throughout the entire stomach. We have also shown by experimental manipulations that the fibers in the stomach originate from VIPLI neurons in the myenteric plexus.

Animals↗

Interstitial cells of Cajal in the guinea-pig gastrointestinal tract as revealed by c-Kit immunohistochemistry.

Interstitial cells of Cajal (ICC) of various morphologies have been described in the gastrointestinal (GI) tracts of mammals. Different classes of ICC are likely to have different functional roles. ICC of the mouse GI tract have been shown to express c-kit, a proto-oncogene that codes for a receptor tyrosine kinase. We have studied the distribution of ICC within the guinea pig GI tract using antibodies to c-Kit protein and immunohistochemical techniques. c-Kit-like immunoreactivity revealed at least 6 types of ICC: (1) intramuscular ICC (IC-IM1) that lie within the muscle layers of the esophagus, stomach, and cecum, (2) ICC within the myenteric plexus region (IC-MY1) in the corpus, antrum, small intestine, and colon, (3) ICC that populate the deep muscular plexus of the small intestine (IC-DMP), (4) ICC at the submucosal surface of the circular muscle layer in the colon (IC-SM), (5) stellate ICC that are closely associated with the myenteric plexus (IC-MY2) and orientated toward the longitudinal muscle layer in the colon, and (6) branching intramuscular ICC (IC-IM2) in the proximal colon within the circular and longitudinal muscle layers. c-Kit immunohistochemistry appears to be an excellent and selective technique for labeling ICC of the guinea-pig GI tract. Labeling of these cells at the light-microscopic level provides an opportunity for characterizing the distribution, density, organization, and relationship between ICC and other cell types.

Animals↗

Characterization of opioid receptors modulating neurogenic contractions of circular muscle from porcine ileum and evidence that delta- and kappa-opioid receptors are coexpressed in myenteric neurons.

Opioid receptors (ORs) in the myenteric plexus mediate the antimotility actions of opioids in the small intestine. In this study, ORs modulating neurogenic circular muscle contractions in the porcine ileum were characterized by pharmacological and immunohistochemical approaches. Circular muscle-myenteric plexus strips manifested tetrodotoxin- and atropine-sensitive contractions during (ON) and after (OFF) electrical field stimulation. The kappa-OR agonists U-50,488H and U-69,593 inhibited ON contractions (pIC(50) = 7.61 and 8.22, respectively). U-69,593 action was inhibited by the kappa-OR antagonist norbinaltorphimine with an antagonist equilibrium constant (K(e)) of 4.2 nM. Selective delta-OR agonists [D-Ala(2)]-deltorphin II, DSLET, DADLE, SNC80, and DPDPE inhibited OFF contractions (pIC(50) = 9.17, 8.63, 8.50, 8.26, and 7.47, respectively). The selective delta-OR antagonist naltriben reduced the inhibitory actions of SNC80 and DSLET with respective K(e) values of 2.3 and 3.0 nM. In addition, norbinaltorphimine inhibited the actions of these agonists with respective K(e) values of 0.7 and 4.2 nM. The mu-OR agonists DAMGO, loperamide, or morphine exhibited relatively low activities in inhibiting ON and OFF contractions. Using primary antisera directed toward cloned opioid receptors, delta-OR immunoreactivity was observed to be localized alone or in combination with kappa-OR immunoreactivity in myenteric neurons; mu-OR immunoreactivity was absent. The results suggest that myenteric delta- and kappa-opioid receptors mediate the antitransit effects of opioids in the porcine small intestine. These receptors may be functionally coupled in a subpopulation of myenteric neurons.

Amino Acid Sequence↗

Distribution of PACAP (pituitary adenylate cyclase-activating polypeptide)-like and helospectin-like peptides in the teleost gut.

Pituitary adenylate cyclase-activating polypeptide (PACAP) and helospectin are two vasoactive intestinal polypeptide (VIP)-related neuropeptides that have recently been demonstrated in the mammalian gut; the aim of this study was to reveal their occurrence and localisation in the gastrointestinal tract, swimbladder, urinary bladder and the vagal innervation of the gut of teleosts, using immunohistochemical methods on whole-mounts and sections of these tissues from the Atlantic cod, Gadus morhua and the rainbow trout, Oncorhynchus mykiss. Both PACAP-like and helospectin-like peptides were present in the gut wall of the two species. Immunoreactive nerve fibres were found in all layers but were most frequent in the myenteric plexus and along the circular muscle fibres. Immunoreactivity was also demonstrated in nerves innervating the swimbladder wall, the urinary bladder and blood vessels to the gut. Immunoreactive nerve cell bodies were found in the myenteric plexus of the gut and in the muscularis mucosae of the swimbladder. In the vagus nerve, non-immunoreactive nerve cells were surrounded by PACAP-immunoreactive fibres. Double staining revealed the coexistence of PACAP-like and helospectin-like peptides with VIP in all visualized nerve fibres and in some endocrine cells. It is concluded that PACAP-like and helospectin-like peptides coexist with VIP in nerves innervating the gut of two teleost species. The distribution suggests that both PACAP and helospectin, like VIP, are involved in the control of gut motility and secretion.

Amino Acid Sequence↗

Immunohistochemical characterization of putative primary afferent (sensory) myenteric neurons in human small intestine.

Pseudouni- or multiaxonal Dogiel type II neurons are the intrinsic primary afferent (sensory) neurons (IPANs) in the guinea pig small intestine. Our aim was to decipher the chemical code of human myenteric type II neurons and to establish their putative vertical projections, i.e., from the myenteric plexus to the submucosa/mucosa. Additionally, we tried to distinguish them chemically from uniaxonal, dendritic type V neurons displaying, at first glance, similar shapes, i.e., smoothly contoured cell bodies with several long processes. Wholemount preparations of the myenteric plexus were immunohistochemically double or triple stained for neurofilaments (NF) and one or two of the following peptides: calbindin, calretinin (CR), calcitonin gene-related peptide (CGRP), somatostatin (SOM) and substance P (SP). In each triple stained wholemount three counts were conducted: (1) NF-positive pseudouni- or multiaxonal (type II) neurons including their reactivities for the above peptides, (2) uniaxonal or NF-negative neurons displaying coreactivities for the above peptides and (3) NF-reactive type V neurons taking into account their reactivities for the above markers. Additionally, type II neurons, which had an axon leading into (disrupted) interconnecting strands towards the submucosa were counted and somal areas of types II and V neurons were measured. The majority of myenteric type II neurons displayed coreactivities for SOM/CR (89.6%), SOM/SP (86.6%) and SP/CR (81.6%), respectively. A minority of type II neurons was positive for CGRP or calbindin. A small population with type III morphology (uniaxonal, long and slender dendrites) displayed the same coreactivities as type II neurons. In contrast, not one single type V neuron was coreactive for SOM/CR, SOM/SP or SP/CR. Out of 627 type II neurons counted in six wholemounts, 84 type II neurons displayed an axon which could be followed into disrupted interconnecting strands indicating a vertical projection pattern. Somal areas of type II neurons were twice as big as those of type V neurons (904+/-210 versus 449+/-110 microm(2)). In conclusion, most human myenteric type II neurons contain SOM, SP and CR. We suggest they are the human IPANs. Type V neurons are both morphologically and chemically distinctly different from type II neurons and may represent descending interneurons. Further studies have to decipher the type-specific chemical code of type II neurons distinguishing them also from type III neurons.

Adolescent↗

Ruminal muscle of sheep is innervated by non-polarized pathways of cholinergic and nitrergic myenteric neurones.

The motility patterns of the reticulorumen evoke mainly mixing of the ingesta. So far unknown, intrinsic neural circuits of the enteric nervous system are involved in the control of these motility patterns. The aim of the study was to characterize neurochemically sheep ruminal myenteric neurones, in particular the neural pathways innervating the ruminal muscle layers. Cell bodies within the myenteric plexus projecting to the longitudinal or circular muscle layer were retrogradely labelled by direct application of the fluorescent tracer 1,1'-didodecyl-3,3,3',3'-tetramethyl indocarbocyanine perchlorate (DiI) onto the circular or longitudinal muscle. The neurochemical code of myenteric neurones was identified by their immunoreactivity for choline acetyltransferase (ChAT), nitric oxide synthase (NOS), substance P (SP) and vasoactive intestinal peptide (VIP). According to their neurochemical code, ruminal myenteric neurones were divided into three populations: ChAT/SP (68% of all myenteric neurones), NOS/VIP (26% of all myenteric neurones) and ChAT/- (5% of all myenteric neurones). Application of DiI onto the circular or longitudinal muscle revealed on average 64 or 44 labelled cell bodies in the myenteric plexus, respectively. DiI-labelled neurones expressed the code ChAT/SP or NOS/VIP. In the pathways to circular or longitudinal muscle, ChAT/SP-positive neurones outnumbered NOS/VIP-immunoreactive neurones by 5:1 and 2:1. Pathways to the circular or longitudinal muscle did not exhibit any pronounced polarized innervation patterns. This study demonstrated specific projections of myenteric neurones to the ruminal muscle. Neurones expressing the code ChAT/SP might function as excitatory muscle motor neurones, whereas NOS/VIP neurones are likely to act as inhibitory muscle motor neurones.

Animals↗

Passive and active membrane properties of canine gastric antral circular muscles.

Experiments were performed to determine the mechanisms responsible for the gradient of electrical activity within circular muscle of the canine gastric antrum. Cable properties of canine gastric antral circular muscles were determined using the partitioned chamber technique of Abe and Tomita (J. Physiol. Lond. 196: 87-100, 1968). The length constant of the circular muscle near the myenteric plexus was 2.4 mm. This was significantly greater than the length constant of the circular muscle near the submucosa (1.7 mm). Membrane time constants were determined by two techniques. Although the time constant of the circular muscle near the myenteric plexus tended to be greater than that of the circular muscle near the submucosa, this difference was not statistically significant. The two regions of circular muscle also differed in their relative levels of excitability. Submucosal circular muscles demonstrated considerably more outward rectification on depolarization and were difficult to bring to threshold for slow waves. This study demonstrates that significant differences exist in the passive and active membrane properties of myenteric and submucosal circular muscle cells. The data help explain the gradient of electrical activity through the thickness of antral circular muscle.

Animals↗

Lack of intestinal pacemaker (C-KIT-positive) cells in infantile hypertrophic pyloric stenosis.

The pathogenesis of infantile hypertrophic pyloric stenosis (IHPS) is not well understood. Recent studies have shown that the protonocogene c-kit is essential for the development or maintenance of autonomic gut motility, and also show that the c-kit gene protein product (C-KIT) positive cells in the mammalian gut are responsible for intestinal pacemaker activity. This study examines cells in the pyloric muscles of 23 patients (16 with IHPS, 7 controls) for the presence of the C-KIT (C-KIT+), using immunohistochemical techniques with antihuman C-KIT sera. In the controls, many C-KIT immunoreactive (IR+) cells were observed in the muscle layers. The myenteric plexuses were demarcated by a moderate number of C-KIT-IR+ cells. However, in the IHPS patients, C-KIT-IR were either absent or significantly reduced. No C-KIT-IR+ cells were found around the myenteric plexuses. These findings suggest that a lack of c-kit expression (as an indicator of intestinal pacemaker activity) in the hypertrophic pyloric smooth muscles may be an important factor in the pathogenesis of IHPS.

Biological Clocks↗

Different mechanisms of contraction generation in circular muscle of canine colon.

Smooth muscle cells from the circular muscle layer of the dog colon showed a mechanical threshold of -44 mV. No gradient in mechanical threshold was measured between the cells from the submucosal and myenteric plexus surface. The threshold was passed during the upstroke and the plateau phase of the spontaneous slow-wave activity from cells at the submucosal surface and by spike potentials occurring mainly in cells at the myenteric plexus surface and sporadically in cells at the submucosal surface. Carbachol-induced specific changes in electrical and mechanical activities that were inhibited by calcium influx blockade are as follows: 1) increase in slow-wave duration; 2) decrease in plateau potential; 3) enhancement of spiking activity; and 4) increase in contractility. This indicates that calcium influx is significantly increased in the presence of carbachol in cells at both surfaces of the circular muscle layer. The increase in calcium influx could be the result of a direct action by carbachol on the calcium conductance and/or could be mediated by a decrease in outward current. The latter is suggested by the carbachol-induced membrane depolarization associated with an increase in the input resistance, which were both methoxyverapamil insensitive. The results show that an excitatory stimulus can generate contraction of the circular muscle through different electrophysiological activities. In addition, the patterns of spontaneous electrical activity and the different responses to carbachol stimulation provide further information about the heterogeneous nature of the electrical activities within the colonic circular muscle layer.

Animals↗

Enteric nerves and interstitial cells of Cajal are altered in patients with slow-transit constipation and megacolon.

BACKGROUND & AIMS: A variety of gastrointestinal motility disorders have been attributed to alterations of interstitial cells of Cajal and malformations of the enteric nervous system. This study evaluates both the distribution of interstitial cells of Cajal and the pathohistology of the enteric nervous system in 2 severe human colorectal motility disorders. METHODS: Colonic specimens obtained from patients with slow-transit constipation (n = 11), patients with megacolon (n = 6), and a control group (n = 13, nonobstructing neoplasia) were stained with antibodies against c-kit (marker for interstitial cells of Cajal) and protein gene product 9.5 (neuronal marker). The morphometric analysis of interstitial cells of Cajal included the separate registration of the number and process length within the different regions of the muscularis propria. The structural architecture of the enteric nervous system was assessed on microdissected whole-mount preparations. RESULTS: In patients with slow-transit constipation, the number of interstitial cells of Cajal was significantly decreased in all layers except the outer longitudinal muscle layer. The myenteric plexus showed a reduced ganglionic density and size (moderate hypoganglionosis) compared with the control group. Patients with megacolon were characterized by a substantial decrease in both the number and the process length of interstitial cells of Cajal. The myenteric plexus exhibited either complete aganglionosis or severe hypoganglionosis. CONCLUSIONS: The enteric nervous system and interstitial cells of Cajal are altered concomitantly in slow-transit constipation and megacolon and may play a crucial role in the pathophysiology of colorectal motility disorders.

Adult↗

Thrombin and mast cell tryptase regulate guinea-pig myenteric neurons through proteinase-activated receptors-1 and -2.

1. Proteases regulate cells by cleaving proteinase-activated receptors (PARs). Thrombin and trypsin cleave PAR-1 and PAR-2 on neurons and astrocytes of the brain to regulate morphology, growth and survival. We hypothesized that thrombin and mast cell tryptase, which are generated and released during trauma and inflammation, regulate enteric neurons by cleaving PAR-1 and PAR-2. 2. We detected immunoreactive PAR-1 and PAR-2 in > 60 % of neurons from the myenteric plexus of guinea-pig small intestine in primary culture. A large proportion of neurons that expressed substance P, vasoactive intestinal peptide or nitric oxide synthase also expressed PAR-1 and PAR-2. We confirmed expression of PAR-1 and PAR-2 in the myenteric plexus by RT-PCR using primers based on sequences of cloned guinea-pig receptors. 3. Thrombin, trypsin, tryptase, a filtrate from degranulated mast cells, and peptides corresponding to the tethered ligand domains of PAR-1 and PAR-2 increased [Ca2+]i in > 50 % of cultured myenteric neurons. Approximately 60 % of neurons that responded to PAR-1 agonists responded to PAR-2 agonists, and > 90 % of PAR-1 and PAR-2 responsive neurons responded to ATP. 4. These results indicate that a large proportion of myenteric neurons that express excitatory and inhibitory neurotransmitters and purinoceptors also express PAR-1 and PAR-2. Thrombin and tryptase may excite myenteric neurons during trauma and inflammation when prothrombin is activated and mast cells degranulate. This novel action of serine proteases probably contributes to abnormal neurotransmission and motility in the inflamed intestine.

Animals↗

Action of enkephalinergic neurons on the gastrointestinal motility.

The actions of the enkephalinergic neurons in the myenteric plexus on the gastrointestinal motility were studied using the opiate antagonist naloxone in the guinea pig in vitro and in vivo. Naloxone increased or decreased spontaneous contractions of the isolated small intestine. Both responses were abolished by atropine. Naloxone potentiated or inhibited the twitch response to transmural stimulation at a frequency of 0.1 Hz and the contractile response of the ileum to the mesenteric nerve stimulation. Naloxone reversed an inhibition of the twitch response occurred after repetitive transmural stimulation (10 Hz) for 5 minutes in the isolated ileal segment. The peristaltic reflex response in the isolated jejunum induced by its distention was reduced by repeated distention. This reduction was reversed by naloxone. Naloxone also potentiated the contractile response of the stomach to efferent vagal stimulation in vivo. It is concluded from the present results that enkephalinergic neurons in the myenteric plexus may regulate the gastrointestinal motility by inhibiting release of acetylcholine from myenteric cholinergic neurons, and that naloxone has both opiate antagonistic and partial agonistic effects on the gastrointestinal motility of the guinea pig.

Animals↗

Nitric oxide producing neurons in the monkey and human digestive system.

Nitric oxide has been proposed as an inhibitory transmitter molecule that plays a role in muscle relaxation and vasodilation in the gastrointestinal tract. The present study analyzes the distribution of nitric-oxide-producing neurons in the monkey and human digestive system by means of nicotinamide-adenine-dinucleotide-phosphate-diaphorase histochemistry. This histochemical method is reliable and convenient for the visualization of neuronal nitric-oxide synthase, the enzyme responsible for nitric-oxide generation. In the gastrointestinal tract, nitric-oxide-synthase-related diaphorase activity was present in nerve fibers running throughout the muscular layer (circular > longitudinal) and in numerous ganglion cells and processes in the myenteric plexus of monkeys and humans. Labelled ganglion cells and fibers also were observed in the submucous plexus, although they were much less numerous than those seen in the myenteric plexus. In the submucosa, a few positive fibers were seen around blood vessels. In the mucosa, stained fibers were sparse at the base of the villi and crypts, whereas they were quite abundant in the muscularis mucosae, especially in the small intestine and colon. In the gallbladder (human), labelling was found in ganglion cells and processes of the innermost and outermost ganglionated plexuses. Stained fibers also were distributed to the muscular layer and, less abundantly, to the mucosa and vasculature. Labelled fibers were more abundant in the sphincter of Oddi (human) than in the gallbladder. In the monkey and human pancreas, nicotinamide-adenine-dinucleotide-diaphorase staining was seen mainly in ganglion cells and fibers of intrapancreatic ganglia, and in processes running among acini, around ducts and in the stroma. A moderate density of stained fibers also was distributed to the vasculature, whereas the islets showed few positive processes. Finally, double label experiments performed in the pancreas showed that the vast majority of neurons producing nitric oxide are immunoreactive for vasoactive intestinal peptide.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Comparative immunohistochemical demonstration of peptide F- and other enkephalin-containing neurons in the enteric nervous system of the rat.

The immunohistochemical localization of peptide F and the related enkephalins met5-enkephalin (met-enk), leu5-enkephalin (leu-enk), met5-enkephalin-arg6-phe7 (met-enk-arg-phe), and met5-enkephalin-arg6-gly7-leu8 (met-enk-arg-gly-leu) was investigated by means of the indirect immunofluorescence technique in the enteric nervous system of the rat. Peptide F-like immunoreactivity was widely distributed within neuronal structures throughout the gastrointestinal (GI) tract of the rat. Peptide F-containing nerve cell bodies were mainly located in the myenteric plexus, and only rarely were seen in the submucosal plexus. Peptide F-immunoreactive nerve fibers were principally present in the myenteric plexus and circular muscle layer; few were found in the submucosal plexus, longitudinal muscle layer, muscularis mucosa, and mucosa. No peptide F-containing fibers were found associated with blood vessels in the gut. By comparing the distribution of immunoreactive peptide F with other related enkephalins met-enk, leu-enk, met-enk-arg-phe, and met-enk-arg-gly-leu, we observed that there was a remarkable similarity in the distribution of peptide F and other enkephalins in the GI tract. These data, combined with our previous studies, indicate that peptide F may coexist with other related enkephalins in the same neurons of the enteric nervous system. The results suggest that peptide F, a product of the proenkephalin A gene, may play a physiological role within the enteric nervous system.

Animals↗

Effect of Chagas' disease on nitric oxide-containing neurons in severely affected and unaffected intestine.

PURPOSE: The pathophysiology of Chagas' disease is incompletely understood. Neuronal nitric oxide has been cited as a candidate neurotransmitter responsible for relaxation of the internal anal sphincter. Neuronal nicotinamide adenine dinucleotide phosphate diaphorase can be used as a marker for neuronal nitric oxide synthase. This study was designed to examine the alterations of the nitric oxide-containing neurons in the enteric nervous system of the colon of patients who underwent resections for advanced megacolon and to compare these specimens with small-bowel specimens from the same patients and with specimens from control subjects. METHODS: Specimens from resected rectum and extramucosal small-bowel biopsy specimens from 11 patients with Chagas megacolon but no apparent small-bowel clinical involvement were compared with the uninvolved colon and jejunum of 10 control patients with colon cancer. Tissues were fixed in Zamboni solution and evaluated by histochemistry for nicotinamide adenine dinucleotide phosphate diaphorase-containing neurons. Reactivity was evaluated on a 0 to 4 scale in the longitudinal muscle, myenteric plexus, circular muscle, submucosal plexus, and mucosa. RESULTS: Specimens from control patients showed well-stained myenteric and submucosal neurons and an abundant network of terminal nerve fibers in the muscle layers. Chagasic specimens had decreased staining in all layers of the gut. Overall there was a statistically significant decrease in nicotinamide adenine dinucleotide phosphate diaphorase-containing neurons. Biopsy specimens from clinically uninvolved small bowel of patients with Chagas' disease also showed decreased reactivity, but to a lesser degree. CONCLUSIONS: Nicotinamide adenine dinucleotide phosphate diaphorase activity is decreased in patients with advanced megacolon. The alterations are more relevant in the myenteric plexus and the circular muscle. Reactivity is also diminished in the clinically uninvolved small bowel, but to a lesser extent.

Adult↗

Changes in enteric neurone phenotype and intestinal functions in a transgenic mouse model of enteric glia disruption.

AIMS: The influence of enteric glia on the regulation of intestinal functions is unknown. Our aim was to determine the phenotype of enteric neurones in a model of glia alterations and the putative changes in intestinal motility and permeability. METHODS: Transgenic mice expressing haemagglutinin (HA) in glia were used. Glia disruption was induced by injection of activated HA specific CD8+ T cells. Control mice consisted of non-transgenic littermates injected with activated HA specific CD8+ T cells. Immunohistochemical staining for choline acetyltransferase (ChAT), substance P (SP), vasoactive intestinal peptide (VIP), and nitric oxide synthase (NOS) was performed on jejunal submucosal plexus (SMP) and myenteric plexus (MP). Neurally induced jejunal muscle activity was characterised in vitro. Gastrointestinal transit and paracellular permeability were measured using fluorescein isothiocyanate-dextran markers. RESULTS: CD3 positive T cells infiltrates were observed in the MP of transgenic mice. In the SMP, the proportions of VIP and SP positive neurones decreased in transgenic mice compared with control mice. ChAT remained unchanged. In the MP, the proportions of ChAT and NOS positive neurones increased and decreased, respectively, in transgenic mice. In contrast, VIP and SP remained unchanged. Neurally mediated jejunal relaxation was lower in transgenic mice than in controls. This relaxation was reduced by NG-nitro-L-arginine methyl ester in control mice but not in transgenic mice. Gastrointestinal transit was delayed and intestinal permeability increased in transgenic mice compared with control mice. CONCLUSION: Glia disruption induces changes in the neurochemical coding of enteric neurones, which may partly be responsible for dysfunctions in intestinal motility and permeability.

Adoptive Transfer↗

Effects of caerulein on the gastric motility of rats.

The effects of caerulein on gastric motility in urethane-anesthetized rats were studied. Caerulein administered into the lateral cerebral ventricle (i.c.v.) and jugular vein (i.v.) caused predominantly an inhibitory effect on gastric motility but sometimes an excitatory or a biphasic effect. The inhibitory response was reduced after vagotomy and/or splanchnicotomy, or after guanethidine. The remaining inhibitory response was abolished by tetrodotoxin, but was resistant to atropine and guanethidine. The excitatory response was abolished by atropine. Discharges of the gastric branch of the vagus nerve were decreased by i.v. injection of caerulein but increased by i.c.v. injection, whereas those of the splanchnic nerve were increased by both i.v. and i.c.v. injection. These results suggest that caerulein causes an inhibition of gastric motility by centrally stimulating vagal non-adrenergic inhibitory nerves and splanchnic adrenergic nerves and inhibiting vagal cholinergic nerves, and by peripherally stimulating non-adrenergic inhibitory neurons of the myenteric plexus. This peptide causes an excitation by stimulating cholinergic neurons of the myenteric plexus.

Animals↗