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J C Bornstein

Publications and source records attributed to J C Bornstein.

At least 55 records · Page 3Linked to original sources
PubMed1996

Electrophysiological mapping of fast excitatory synaptic inputs to morphologically and chemically characterized myenteric neurons of guinea-pig small intestine.

Neurons within the myenteric plexus of the guinea-pig ileum were impaled using conventional intracellular electrodes. Points of stimulation within the surrounding ganglia and connectives which gave rise to fast excitatory synaptic potentials were mapped using a movable monopolar stimulating electrode. Cells were then injected with the intracellular marker, biocytin, and processed for multiple label immunohistochemistry to reveal their morphologies, chemical contents and, hence, their functional classes. Of 65 neurons belonging to the S electrophysiological class, 53 received fast excitatory synaptic inputs from stimulation at sites at least 2 mm away in a directly circumferential direction. These inputs almost certainly arise from stimulation of the circumferentially-directed axons of the Dogiel type II/AH-neurons, which are thought to be intrinsic sensory neurons. The majority of cells which projected anally and were immunoreactive for nitric oxide synthase (19/25), all neurons which ramified in the tertiary plexus and were identified as longitudinal muscle motor neurons (6/6) and all neurons identified as excitatory motor neurons innervating the circular muscle (12/12) received inputs from these circumferentially-directed pathways. However only one of six descending filamentous interneurons impaled received such inputs, suggesting they may be differentially innervated. The conduction velocities of circumferentially-directed axons giving rise to fast excitatory post synaptic potentials were estimated to be 0.41 +/- 0.10 m/s (mean +/- standard deviation, n = 21). The conduction velocities estimated for longitudinally-directed pathways were 0.55 +/- 0.25 m/s (n = 29). Thus, the majority of myenteric neurons receive fast excitatory synaptic input from putative intrinsic sensory neurons which project circumferentially around the intestine.

Animals↗
PubMed1996

Experimental basis for realistic large-scale computer simulation of the enteric nervous system.

1. The enteric nervous system is perhaps the most accessible part of the mammalian nervous system in which it is feasible to attempt large scale computer simulation that is based closely on experimentally determined data. Here we summarize the data obtained for simulation of motility reflexes in the guinea-pig small intestine. 2. The chemistry, morphology and connectivity of each type of neuron involved in intrinsic reflexes have been investigated and most classes of neurons are physiologically well characterized. This includes primary sensory neurons, ascending and descending interneurons and motor neurons to circular and longitudinal muscle. 3. The responses of primary sensory neurons and the physiology of synaptic transmission from sensory neurons to interneurons and motor neurons, from interneurons to interneurons and from interneurons to motor neurons have been recorded during reflexes and in some cases the pharmacology of transmission has also been investigated. 4. Computer simulation, in which the activities of up to 30,000 neurons are modelled, produces patterns of activity that closely mimic those recorded in physiological experiments.

Animals↗
PubMed1996

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

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 guinea pig 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 microM) and by 30% and 45%, respectively, by a desensitizing concentration of the selective NK3 receptor agonist, senktide (1 microM), in the chamber in which reflexes were initiated. Together, hexamethonium and senktide abolished responses to compression. A residual response to distension persisted. This was abolished by hyoscine (1 microM). 3. Hexamethonium (200 microM) 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 microM) in the stimulus chamber reduced distension reflexes to the same extent as synaptic blockade, whereas hexamethonium (200 microM) and hyoscine (1 microM) 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 microM) had no effect and hyoscine (1 microM) reduced only the responses to distension (by 30%). Senktide (1 microM) depressed responses to both stimuli by approximately 80%. 6. Application of hexamethonium (200 microM) 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 microM) or senktide (1 microM) 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 and NK3 receptor-dependent components, transmission from descending interneurones to inhibitory motor neurones is neither cholinergic nor due to tachykinins acting via NK3 receptors.

Acetylcholine↗
PubMed1995

Plurichemical transmission and chemical coding of neurons in the digestive tract.

The enteric nervous system contains neurons with well-defined functions. However, when neurons of the same function are examined in different regions or species, they are found to show subtle differences in their pharmacologies of transmission and different chemical coding. Individual enteric neurons use more than one transmitter, i.e., transmission is plurichemical. For example, enteric inhibitory neurons have three or more primary transmitters, including nitric oxide, vasoactive intestinal peptide, and possibly adenosine triphosphate and pituitary adenylyl cyclase activating peptide. Primary transmitters are highly conserved, although their relative roles vary considerably between gut regions. Multiple substances, including transmitters and their synthesizing enzymes and nontransmitters (such as neurofilament proteins), provide neurons with a chemical coding through which their functions and projections can be identified. Although equivalent neurons in different regions have the same primary transmitters, other chemical markers differ substantially. Caution must be taken in extrapolating pharmacological and neurochemical observations between species or even between regions in the one species. On the other hand, careful interregion and interspecies comparisons lead to an understanding of the features of enteric neurons that are highly conserved and can be used in valid extrapolation.

Animals↗
PubMed1995

Identification of sensory nerve cells in a peripheral organ (the intestine) of a mammal.

It is commonly believed that the cell bodies of mammalian sensory neurons are contained within spinal and cranial sensory ganglia associated with the central nervous system or within the central nervous system itself. However, strong circumstantial evidence implies that some sensory neurons are contained entirely within the gastrointestinal tract. We have investigated this possibility by using intracellular methods to record the responses of myenteric neurons in the guinea-pig small intestine to physiological stimuli applied to the neighbouring mucosa. The results show that the myenteric plexus contains a population of chemosensitive sensory neurons and that these neurons correspond to neurons with AH electrophysiological properties and Dogiel type II morphology. This is the first direct evidence that some sensory neurons are contained entirely within the peripheral nervous system.

Action Potentials↗
PubMed1995

Evidence that enteric motility reflexes can be initiated through entirely intrinsic mechanisms in the guinea-pig small intestine.

Although motility reflexes can be elicited in the intestine in vivo after all neural connections with the central nervous system are cut, or in vitro in isolated intestinal segments, it is not proven that the cell bodies of the primary sensory neurons for these reflexes are in the intestinal wall. It is feasible that the nerve cells are in dorsal root ganglia and that axon reflexes are involved in the initiation of the reflexes. We have examined reflexes in segments of guinea-pig intestine in which extrinsic denervation, 9-11 days before the intestine was removed, and isolation of the intestine in vitro were combined. The experimental segments were isolated from extrinsic inputs by severing nerves in the mesentery and those running in the gut wall that entered the segment. The effectiveness of denervation was confirmed histochemically. Ascending and descending reflexes were evoked by mucosal distortion or distension and responses were recorded by intracellular microelectrodes in the circular muscle. Reflex responses recorded after denervation were no different to those recorded from control tissue. It is concluded that, in the small intestine of the guinea-pig, cell bodies of primary sensory neurons for mucosal and probably for distension reflexes are intrinsic to the organ.

Animals↗
PubMed1995

Pharmacological evidence that nitric oxide may be a retrograde messenger in the enteric nervous system.

1. The effects of inhibition of nitric oxide synthase on neuro-neuronal and neuromuscular transmission during motility reflexes in the small intestine of the guinea-pig were examined. 2. Isolated segments of intestine were secured in a three chambered organ bath so that different parts of the reflex pathways could be independently exposed to drug-containing solutions. Reflexes were evoked by distension or compression of the mucosa in two adjacent chambers and reflex responses were recorded from the circular muscle with intracellular microelectrodes in the third chamber. Thus, the actions of drugs at connections between sensory neurones and interneurones, between interneurones and other interneurones and at motor neurones could be distinguished. 3. NG-monomethyl-L-arginine (L-NMMA; 100 microM), an inhibitor of nitric oxide synthase, did not affect the ascending excitatory reflex when added to either the central stimulation chamber or the recording chamber. 4. In contrast, L-NMMA (100 microM) enhanced the descending inhibitory reflex when added to the chamber in which stimuli were applied. This effect was prevented by prior exposure to L-arginine (100 microM), which had no effect by itself. Conduction of reflexes between the stimulus chamber and the recording chamber was unaffected by the presence of L-NMMA in an intervening chamber. 5. L-NMMA (100 microM) added to the recording chamber depressed the descending inhibitory reflex, an effect that was prevented by previous exposure to L-arginine. 6. The nitric oxide donor, sodium nitroprusside (100 microM), added to the stimulus chamber, depressed both ascending excitatory and descending inhibitory reflexes. When added to the middle chamber,sodium nitroprusside had no effect on conduction of reflexes through this chamber.7. It is deduced that nitric oxide, released from the cell bodies of descending interneurones, suppresses transmission from synaptic connections made with them by enteric sensory neurones.

Amino Acid Oxidoreductases↗
PubMed1995

Cholinergic, somatostatin-immunoreactive interneurons in the guinea pig intestine: morphology, ultrastructure, connections and projections.

The shape, projection, ultrastructure and chemistry of interneurons that were initially identified by their immunoreactivity for somatostatin in the small intestine of the guinea pig were examined. Somatostatin immunoreactive nerve cell bodies and nerve fibres were located in the myenteric plexus. Simultaneous labelling for 2 antigens revealed that the somatostatin immunoreactive interneurons were also immunoreactive for choline acetyltransferase, but not for calbindin or neuropeptide Y. Cell shapes were determined by immunohistochemistry, ultrastructural analysis and intracellular dye filling. The neurons had large cell bodies (38 x 14 microns) which gave rise to long branched filamentous dendrites and a single axon. The projections of the somatostatin immunoreactive interneurons were determined by analysis of patterns of fibre loss and survival following degenerative section of myenteric nerve pathways and by analysis of individual neurons that were injected intracellularly with dye. The axons projected anally, sometimes after a short oral excursion, and were confined to the myenteric plexus. They gave rise to multiple varicose branches within myenteric ganglia: in the majority of cases the first branch was within 100 microns of the cell body. Synaptic inputs to the cells were examined by light and electron microscopy. All somatostatin immunoreactive neurons received numerous somatostatin immunoreactive inputs on the cell body and all filamentous processes. Ultrastructural investigation indicated that these constituted the majority of all inputs. It is concluded that cholinergic, somatostatin immunoreactive, interneurons have a unique soma morphology and form synaptically connected chains that run anally in the myenteric plexus.

Animals↗
PubMed1994

Characterization of 5-HT receptors mediating contraction and relaxation of the longitudinal muscle of guinea-pig distal colon in vitro.

A range of agonists and antagonists were used to characterize the receptors through which 5-hydroxytryptamine (5-HT) contracts and relaxes the longitudinal muscle of segments of guinea-pig distal colon, in vitro. 5-HT contracted the longitudinal muscle over the concentration range 10(-9) to 10(-4) mol/l. The 5-HT3 receptor agonist, 2-methyl-5-HT, produced concentration dependent contractions over the range 10(-6) to 10(-4) mol/l. 5-methoxytryptamine, an agonist at 5-HT4 receptors, caused contractions over a concentration range of 10(-8) to 10(-4) mol/l. The 5-HT4 antagonist, SDZ 205-557 (5 x 10(-7) mol/l) substantially suppressed the responses to low concentrations of 5-HT and to 5-methoxytryptamine, but had no effect on the responses to higher concentrations of 5-HT. In contrast, the 5-HT3 antagonist, granisetron (10(-6) mol/l), blocked the effect of 2-methyl-5-HT and substantially depressed responses to high concentrations of 5-HT, but had no effect on lower concentrations of 5-HT. Granisetron produced a small reduction in the response to 5-methoxytryptamine. Tetrodotoxin (TTX) (3 x 10(-7) mol/l) almost abolished the response to 5-methoxytryptamine and markedly suppressed the response to 2-methyl-5-HT, but the responses to 5-HT were only partially reduced. The 5-HT1 antagonist, methiothepin (10(-6) mol/l) depressed the response to 5-HT (10(-7) to 10(-4) mol/l) and blocked its TTX insensitive component. The 5-HT2 antagonist, ketanserin, in concentrations up to 10(-5) mol/l, had no effect on the contractions evoked by 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Calretinin-immunoreactive neurons and their projections in the guinea-pig colon.

The distribution of nerve cells and fibres with immunoreactivity for the calcium-binding protein, calretinin, was studied in the distal colon of the guinea-pig. The projections of the neurons were determined by examining the consequences of lesioning the myenteric plexus. Calretinin-immunoreactive neurons comprised 17% of myenteric nerve cells and 6% of submucous nerve cells. Numerous calretinin-immunoreactive nerve fibres were located in the longitudinal and circular muscle, and within the ganglia of the myenteric and submucous plexuses. Occasional fibres were found in the muscularis mucosae, but they were very rare in the lamina propria of the mucosa. Lesion studies revealed that myenteric neurons innervated the underlying circular muscle and provided both ascending and descending processes that gave rise to varicose branches in myenteric ganglia. Calretinin-immunoreactive fibres also projected to the tertiary component of the myenteric plexus, and are therefore likely to be motor neurons to the longitudinal muscle. Varicose fibres that supplied the submucous ganglia appear to arise from submucous nerve cells. Arterioles of the submucous plexus were sparsely innervated by calretinin-immunoreactive fibres. The submucous plexus was the principal source of immunoreactive nerve fibres in the muscularis mucosae. This work shows that calretinin-IR reveals different neuronal populations in the large intestine to those previously reported in the small intestine.

Animals↗
PubMed1994

Projections of 5-hydroxytryptamine-immunoreactive neurons in guinea-pig distal colon.

The presence of 5-hydroxytryptamine in enteric neurons of the guinea-pig distal colon was demonstrated by immunohistochemistry and the projections of the neurons were determined. 5-Hydroxytryptamine-containing nerve cells were observed in the myenteric plexus but no reactive nerve cells were found in submucous ganglia. Varicose reactive nerve fibres were numerous in the ganglia of both the myenteric and submucous plexuses, but were infrequent in the longitudinal muscle, circular muscle, muscularis mucosae and mucosa. Reactivity also occurred in enterochromaffin cells. Lesion studies showed that the axons of myenteric neurons projected anally to provide innervation to the circular muscle and submucosa and to other more anally located myenteric ganglia. The results suggest that a major population of 5-hydroxytryptamine neurons in the colon is descending interneurons, most of which extend for 10 to 15 mm in the myenteric plexus and innervate both 5-hydroxytryptamine and non-5-hydroxytryptamine neurons.

Animals↗
PubMed1994

Charybdotoxin and iberiotoxin but not apamin abolish the slow after-hyperpolarization in myenteric plexus neurons.

Myenteric neurons of guinea-pig ileum were studied with intracellular microelectrodes. The specific toxins charybdotoxin, iberiotoxin and apamin were used to characterize the prolonged after-hyperpolarizations of AH neurons in this preparation. Charybdotoxin and iberiotoxin blocked prolonged after-hyperpolarizations in 23 of 24 AH neurons, but apamin had no effect on 5 of 5 AH neurons. Abolition of the after-hyperpolarizations was accompanied by depolarization and increases in input resistances of those AH neurons affected, but the shapes of action potentials were unchanged. The excitability of the AH neurons was enhanced as shown by an increase in the number of action potentials evoked by a 500-ms depolarizing current pulse or by a train of 15-ms depolarizing current pulses (10Hz). The other class of myenteric neurons, S neurons, was also investigated. The 19 S neurons studied fired action potentials only at the start of a 500 ms depolarization, but the toxins had no effect on this behaviour or on their other properties. Intracellular injection of Neurobiotin into the neurons studied and subsequent immunohistochemical staining to localise the calcium-binding protein, calretinin, indicated that all major classes of S neurons were included in the sample. Thus, the prolonged after-hyperpolarizations in AH neurons may be due to opening of a large-conductance (BK) calcium-dependent potassium channel, but similar channels play little or no role in regulation of the excitability of S neurons.

Animals↗
PubMed1994

Combined intracellular injection of Neurobiotin and pre-embedding immunocytochemistry using silver-intensified gold probes in myenteric neurons.

We have developed methods to examine the neurochemistry of synaptic inputs to individual myenteric neurons labeled by dye injection through intracellular recording electrodes. Myenteric neurons of the guinea-pig ileum were filled with Neurobiotin, fixed, washed in 50% ethanol, exposed to sodium cyanoborohydride, incubated in avidin-biotin-horseradish peroxidase and incubated in antisera to calretinin or calbindin. The Neurobiotin-filled cells were revealed using the diaminobenzidine (DAB) reaction. The tissue was examined at the light microscope level to determine the morphology and projections of the Neurobiotin-filled neurons, and then incubated in 1 nm gold-labeled secondary antibodies. Following osmication, the gold probes were silver-intensified and the tissue embedded flat in resin. The tissue was re-examined at the light microscope level. Neurons containing a DAB reaction product could be distinguished from neurons containing a silver-intensified gold reaction product using oblique or epipolarized illumination. Ultrathin sections were taken through the injected neurons and examined. At the ultrastructural level, Neurobiotin-filled cell bodies and their processes (labeled with DAB) were easily distinguished from the structures labeled by silver-intensified gold. Gold-labeled terminals of enteric interneurons made synapses and close contacts with Neurobiotin-filled nerve cell bodies and their processes. This technique is valuable for the neurochemical identification of synaptic inputs to morphologically and/or functionally characterized myenteric neurons and could be easily applied to other preparations, such as brain slices.

Animals↗
PubMed1994

Electrophysiological and morphological classification of myenteric neurons in the proximal colon of the guinea-pig.

Intracellular recordings were made from myenteric neurons in the proximal colon of the guinea-pig. The electrical behaviour of the neurons in response to intracellular depolarizing current pulses, and to internodal strand stimulation, was recorded. The intracellular electrode contained the intracellular marker biocytin which was injected into impaled neurons for subsequent histochemistry. Proximal colon myenteric neurons displayed electrophysiological properties similar to myenteric neurons in the small intestine, and were classified as either AH- or S-neurons. AH-neurons were characterized by the presence of a slow afterhyperpolarization following an action potential. Internodal strand stimulation evoked slow excitatory synaptic potentials in five out of six AH-neurons tested, but did not evoke fast excitatory synaptic potentials in 26 AH-neurons tested. S-neurons lacked a slow afterhyperpolarization, but internodal strand stimulation evoked fast excitatory synaptic potentials in all 113 neurons and slow excitatory synaptic potentials in seven out of 17 tested. A subpopulation of AH-neurons displayed a rhythmic oscillation in membrane potential which could be triggered by an action potential. S-neurons could be subdivided into those that fired tonically and those that fired phasically in response to long depolarizing current pulses. About 80% of the AH-neurons were immunoreactive for calbindin, as were 10% of S-neurons. A further 17% of S-neurons, but no AH neurons, were calretinin immunoreactive. Morphological analysis of filled neurons revealed eight distinct classes. Neurons electrophysiologically classified as AH typically had a large, oval soma and several long tapering processes. Processes of AH-neurons branched into many adjacent ganglia. Almost all S-neurons were uniaxonal and many axons ended in an expansion bulb in the myenteric plexus. S-neurons typically had broad, lamellar processes, or short, spiny processes. Roughly equal proportions of S-neurons had oral or anal projection. However, almost all S-neurons that were immunoreactive for calbindin or calretinin projected orally. The results indicate that myenteric neurons in the proximal colon of the guinea-pig are electrophysiologically similar to myenteric neurons in the small intestine, but there are a greater number of morphological and chemical categories.

Action Potentials↗
PubMed1994

Local neural control of intestinal motility: nerve circuits deduced for the guinea-pig small intestine.

1. Propulsion of digesta along the intestine appears to occur by the action of a series of local reflexes which cause contraction oral to the digesta and relaxation of circular muscle on the anal side. 2. There is now substantial evidence available about the identities of the enteric neurons that mediate these reflexes. 3. The motor neurons and interneurons of the reflex pathways lie within the myenteric plexus. These neurons can be classified electrophysiologically as S-neurons and have distinctive projections and neurochemistries. 4. The sensory neurons may lie in the myenteric plexus, but there is some evidence for sensory neurons in the submucous plexus. A contribution from extrinsic sensory neurons to local motility reflexes cannot be ruled out. Intrinsic sensory neurons are probably AH-neurons and are large multi-axonal cells.

Animals↗
PubMed1994

Investigation of the role of 5-HT3 and 5-HT4 receptors in ascending and descending reflexes to the circular muscle of guinea-pig small intestine.

1. The present study was undertaken to ascertain whether 5-hydroxytryptamine (5-HT) acting at either 5-HT3 or 5-HT4 receptors plays a significant role in motility reflexes in the guinea-pig small intestine. 2. An isolated segment of small intestine was opened along its mesenteric border and pinned, mucosa uppermost, in a three chambered organ bath so that the oral, middle and anal regions of a single preparation could be separately superfused. 3. Conventional intracellular recording methods were used to monitor the responses of the circular muscle in the oral or the anal end chambers when distension was applied in either of the other two chambers or the mucosal villi were compressed in the middle chamber. Drugs were added to the middle chamber. 4. 5-HT3 receptor antagonists (tropisetron, 0.1-10 microM; granisetron, 1 microM and BRL 46470, 1 microM) depressed the ascending excitatory reflex evoked by these stimuli but had no effect on the descending inhibitory reflex. The depression of the excitatory reflex was observed whether the reflex was evoked from the chamber containing the drug or was simply conducted, via interneurones, through this chamber. 5. The 5-HT4 receptor antagonist, SDZ 205-557 (1 microM), had no significant effect on either the ascending or descending reflex pathways. However, 5-HT4 receptors were present as cisapride (0.1 microM) significantly enhanced the ascending excitation without affecting the descending inhibition. This effect of cisapride was converted to a significant depression of the ascending reflex by SDZ 205-557. 6. The results suggest that 5-HT3, but not 5-HT4, receptors play an important role in the ascending excitatory reflex and that these receptors may be on interneurones in the reflex pathway.

4-Aminobenzoic Acid↗
PubMed1994

Characterization of 5-hydroxytryptamine receptors mediating mucosal secretion in guinea-pig ileum.

1. The receptor subtypes through which 5-hydroxytryptamine (5-HT) increases electrolyte secretion across the mucosa of guinea-pig ileum were studied. 2. Flat sheep preparations of guinea-pig mucosa plus submucosa were placed in Ussing chambers and the short circuit current (ISC), an index of net electrogenic electrolyte transport across the mucosa, was measured under voltage clamp conditions. 3. Low concentrations of 5-HT (10-300 nM) evoked monophasic increases in ISC which were significantly reduced by hyoscine (100 nM), tetrodotoxin (TTX, 300 nM) and the 5-HT2 receptor antagonist, ketanserin (3-300 nM). 4. Higher concentrations of 5-HT (1-10 microM) produced biphasic responses which were reduced by hyoscine (100 nM), TTX (300 nM), ketanserin (3-300 nM) and also by the 5-HT3 receptor antagonists, granisetron (1 microM) and ICS 205-930 (100 nM). 5. 2-Methyl-5-HT (1-100 microM) and alpha-methyl-5-HT (30 nM-30 microM), agonists at 5-HT3 and 5-HT2 receptors respectively, also evoked ISC increases. These responses were reduced by hyoscine (100 nM) and abolished by TTX (300 nM) and the respective receptor antagonists, granisetron (1 microM) and ketanserin (30 nM). 6. The 5-HT4 receptor antagonist, SDZ 205-557 (300 nM) had no effect on the response to 5-HT. 7. The TTX-resistant response to 5-HT was not affected by 5-HT2,3 or 4 receptor antagonists. 8. These results indicate that 5-HT mediates secretion partly by an action on 5-HT3 receptors located on cholinergic and noncholinergic secretomotor neurones, partly by an action on higher affinity'5-HT2-like' receptors predominantly on noncholinergic neurones, and partly by a direct action on the epithelium.

Animals↗