Search PubMed⌕ Search

Biomedical subjects

J B Furness

Publications and source records attributed to J B Furness.

At least 163 records · Page 9Linked to original sources
PubMed1990

Calbindin neurons of the guinea-pig small intestine: quantitative analysis of their numbers and projections.

The distribution of nerve cells with immunoreactivity for the calcium-binding protein, calbindin, has been studied in the small intestine of the guinea-pig, and the projections of these neurons have been analysed by tracing their processes and by examining the consequences of nerve lesions. The immunoreactive neurons were numerous in the myenteric ganglia; there were 3500 +/- 100 reactive nerve cells per cm2 of undistended intestine, which is 30% of all nerve cells. In contrast, reactive nerve cells were extremely rare in submucous ganglia. The myenteric nerve cells were oval in outline and gave rise to several long processes; this morphology corresponds to Dogiel's type-II classification. Processes from the cell bodies were traced through the circular muscle in perforating nerve fibre bundles. Other processes ran circumferentially in the myenteric plexus. Removal of the myenteric plexus, allowing time for subsequent fibre degeneration, showed that reactive nerve fibres in the submucous ganglia and mucosa came from the myenteric cell bodies. Operations to sever longitudinal or circumferential pathways in the myenteric plexus indicated that most reactive nerve terminals in myenteric ganglia arise from myenteric cell bodies whose processes run circumferentially for 1.5 mm, on average. It is deduced that the calbindin-reactive neurons are multipolar sensory neurons, with the sensitive processes in the mucosa and with other processes innervating neurons of the myenteric plexus.

Animals↗
PubMed1990

Ultrastructure and synaptology of neurons immunoreactive for gamma-aminobutyric acid in the myenteric plexus of the guinea pig small intestine.

Immunoreactivity for gamma-aminobutyric acid is located in one morphologically-defined class of nerve cell body in the myenteric plexus of the guinea pig small intestine. These are a subgroup of the Dogiel type I nerve cells, characterized by their lamellar dendrites, about 1 micron thick and flattened in the plane of the myenteric plexus, and one (or rarely two) long axonal process that extends to either the longitudinal or the circular muscle. At an ultrastructural level the dendrites were characterized by their open cytoplasm in which were scattered granular vesicles, pale mitochondria, Golgi apparatus and endoplasmic reticulum. A large proportion of the dendritic surface was in direct contact with the extra-ganglionic space. In the cell body region, which was away from the ganglion surface, the nucleus was surrounded by a thin rim of cytoplasm. The cytoplasmic features are quite distinct from those of Dogiel type II neurons but they were shared by many other non-immunoreactive neurons. Synaptic inputs, which were all non-immunoreactive, were found on the dendrites, cell bodies, axon hillocks and axons of the gamma-aminobutyric acid-immunoreactive neurons. The predominant vesicle type in the presynaptic elements was the small clear vesicle, 40-60 nm in diameter. Based on two gamma-aminobutyric acid-immunoreactive cells that were examined in serial section, about 40-50% of synapses are dendritic, 20-25% are somatic, and 30-35% are on the axon hillock or first 50-70 microns of the axon. No synapses formed by immunoreactive varicosities were found on non-immunoreactive neurons or in the neuropil of the myenteric ganglia. Moreover, the lamellar dendrites or soma of gamma-aminobutyric acid neurons were never presynaptic elements forming relationships with other elements in the ganglia. It is concluded that the gamma-aminobutyric acid reactive Dogiel type I neurons are motor neurons providing inputs to the circular and longitudinal muscle layers.

Animals↗
PubMed1990

Distribution and actions of galanin and vasoactive intestinal peptide in the human colon.

Responses to galanin (GAL) and vasoactive intestinal peptide (VIP) and their distribution were investigated in muscularis externa from the human sigmoid colon. Immunohistochemical studies revealed GAL-like immunoreactivity (GAL-IR) and VIP-IR in nerve fibres supplying both muscle layers as well as the myenteric ganglia. Additionally GAL-IR was shown to co-exist with VIP-IR in many nerve fibres innervating human circular and longitudinal (taenial) colonic muscle layers. Circular and longitudinal muscle strips were contracted by GAL and relaxed by VIP. There was a marked difference in sensitivity between muscle layers to both peptides; circular muscle being less sensitive to GAL, longitudinal muscle less sensitive to VIP. When given simultaneously GAL attenuated responses to VIP on longitudinal muscle, thus in the same neurone there are substances having opposing actions on smooth muscle motility.

Colon↗
PubMed1990

Distension-evoked ascending and descending reflexes in the circular muscle of guinea-pig ileum: an intracellular study.

Reflex responses evoked by distension of the guinea-pig small intestine were recorded from the circular muscle with intracellular microelectrodes. For this purpose a mechanically stable preparation that allowed the intestinal wall to be distended within 9 mm of the recording site was developed. A segment of intestine was opened along the mesenteric border and pinned mucosa uppermost over a balloon set in the base of an organ bath, so that inflation of the balloon could distend the intestinal wall without simultaneously pushing against the mucosa. Compound excitatory junction potentials (EJPs) and compound inhibitory junction potentials (IJPs) were recorded at sites up to 40 mm oral and anal to the distending stimulus, respectively. The compound EJPs recorded orally had amplitudes of up to 24 mV and declined to baseline during distensions that exceeded 10-15 s. Distensions at intervals of less than 20 s evoked successively smaller oral compound EJPs; after four distensions in 30 the amplitude of the compound EJP had fallen to less than 10%. The amplitude of the oral compound EJP was reduced by hyoscine (1 microM), but the extent of the reduction depended on the degree of distension; responses to mild stimuli were blocked, whereas those to strong stimuli were only slightly reduced. The amplitude of the hyoscine-resistant component of the compound EJP was markedly reduced by antagonists of substance P receptors in the muscle. In the presence of muscarinic and substance P receptor antagonists, a transient compound IJP could be detected on the oral side of the stimulus. The compound IJPs recorded anal to the distension had amplitudes up to 22 mV but the potential returned to baseline during prolonged distension. In the presence of hyoscine (1 microM) some inhibitory activity continued throughout prolonged stimuli. Compound IJP amplitudes were not significantly reduced by repeated distensions separated by more than 6 s. At anal sites a transient depolarization (off-response) was recorded immediately following the termination of a distension in some preparations. The off-response was unaffected by hyoscine and was more readily observed after the further addition of substance P antagonists. The compound IJPs were almost completely blocked by apamin (0.2 microM). The compound EJPs and IJPs recorded orally were blocked by hexamethonium (100 microM), but the amplitudes of compound IJPs recorded anally were significantly reduced by hexamethonium (100-200 microM) only at recording sites greater than 15 mm from the centre of the balloon. The off-response was reduced by hexamethonium at all sites.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Morphological and chemical identification of neurons that project from the colon to the inferior mesenteric ganglia in the guinea-pig.

Labelled nerve cells were located in the distal colon of the guinea-pig 4-5 days after the retrograde tracing agent, Fast blue, was injected into the inferior mesenteric ganglia. Labelled neurons were only found in the myenteric plexus. Their frequency increased from oral to anal and was greater towards the mesenteric border, compared with the anti-mesenteric aspect, of the colon. Many retrogradely labelled neurons were immunoreactive for vasoactive intestinal peptide or calbindin. In the inferior mesenteric ganglia, vasoactive intestinal peptide and calbindin immunoreactive nerve fibres surrounded the same clumps of nerve cell bodies. Almost all calbindin and vasoactive intestinal peptide immunoreactive terminals degenerated after the nerves running from the large intestine to the inferior mesenteric ganglia were cut. It is concluded that the great majority of calbindin and vasoactive intestinal peptide immunoreactive terminals in the inferior mesenteric ganglia arise from nerve cell bodies in the myenteric plexus of the large intestine.

Amidines↗
PubMed1990

Projections of substance P, vasoactive intestinal peptide and tyrosine hydroxylase immunoreactive nerve fibres in the canine intestine, with special reference to the innervation of the circular muscle.

Antisera raised against neuron specific enolase (NSE), substance P, vasoactive intestinal peptide (VIP) and tyrosine hydroxylase (TH) were used to reveal nerve fibres in the wall of the canine small and large intestine. The circular muscle of the colon was innervated by nerve fibre bundles that ran parallel to the muscle throughout its thickness. A plexus of fibre bundles was found against the inner (submucosal) surface of the circular muscle. Fibres with substance P, VIP and TH immunoreactivity all contributed to this innervation. The circular muscle of the small intestine was distinctly separated into outer and inner layers by a dense plexus of nerve fibres, the deep muscular plexus. The outer and inner circular muscle were innervated by substance P, VIP and TH fibres. Extrinsic denervation through the severing of nerve fibres in the mesentery caused TH fibres in the intestine to degenerate, but had no detectable effect on the fibres with substance P or VIP immunoreactivity. Myectomy (the removal of the myenteric plexus from the full circumference of the intestine over a distance of 2-3 cm), performed 7-13 days before tissue was taken, resulted in an almost complete loss of substance P fibres from the circular muscle of the colon and the outer circular muscle of the small intestine. However, many fibres persisted in the deep muscular plexus of the small intestine, and most fibres remained in its inner circular muscle. The changes in distribution of VIP fibres were almost identical, except that a small proportion of reactive fibres remained in the circular muscle of the colon and the outer circular muscle of the small intestine. It is concluded that the circular muscle layers of the small intestine and colon have dual sources of intrinsic nerve supply: the myenteric ganglia supply fibres primarily to the outer part of the muscle and the submucous ganglia supply fibres to the inner muscle. The present study further demonstrated that VIP fibres ran anally in the myenteric plexus of both the small and large intestine, whereas substance P fibres ran orally in the large intestine and both orally and anally in the small intestine. The innervation of the muscularis mucosae and mucosa by substance P and VIP fibres was not affected by myectomy or extrinsic denervation, and these structures are therefore likely to be innervated by nerve cells in the submucous ganglia.

Animals↗
PubMed1990

Projections of chemically-specified neurons in the guinea-pig colon.

The arrangement of the enteric nerve plexuses in the colon of the guinea-pig and the distributions and projections of chemically specified neurons in this organ have been studied. Immunoreactivity for neuron specific enolase was used to examine the total population of neurons and individual subpopulations were studied using antibodies raised against calbindin, calcitonin gene-related peptide (CGRP), leu-enkephalin, gastrin releasing peptide (GRP), galanin, gamma aminobutyric acid, neurokinin A, neuropeptide Y (NPY), somatostatin, substance P, tyrosine hydroxylase and vasoactive intestinal peptide (VIP). Neuronal pathways within the colon were lesioned using myotomy and myectomy operations and extrinsic pathways running between the inferior mesenteric ganglia and the colon were also severed. Each of the antibodies revealed nerve cells and nerve fibres or only nerve fibres within the wall of the colon. VIP, galanin and GRP were in anally projecting pathways in the myenteric plexus, as they are in other species. In contrast, there are differences in the projection directions of enkephalin, substance P, NPY and somatostatin nerve fibres between regions and species. Surprisingly, somatostatin and NPY fibres have opposite projections in the small intestine and colon of the guinea-pig. The majority of nerve fibres that innervate the circular muscle, including fibres with immunoreactivity for VIP, enkephalin, substance P, NPY, galanin and GRP come from the myenteric ganglia. The mucosa is innervated by fibres from both the myenteric and submucous ganglia. The present results suggest that the guinea-pig distal colon is a suitable place in which to determine relations between structure, neurochemistry and functions of enteric neural circuits.

Animals↗
PubMed1989

Shapes and projections of neurons with immunoreactivity for gamma-aminobutyric acid in the guinea-pig small intestine.

The distribution of nerve cell bodies and fibres with immunoreactivity for gamma-aminobutyric acid (GABA) has been studied in the guinea-pig small intestine. Cell bodies were common in myenteric ganglia but were extremely rare in the submucosa. Reactive fibres were numerous in the tertiary component of the myenteric plexus and in the circular muscle but they were rare in both myenteric and submucous ganglia. Reactive nerve fibres were absent from the mucosa. This distribution conforms to previous descriptions. Exposure to exogenous GABA, in vitro, was used to supplement endogenous stores of GABA. The morphology of cell bodies was better defined after this treatment. Nearly all cell bodies had type-I morphology, i.e., the cells had numerous short lamellar dendrites and one axon. Most axons ran anally. Some could be traced to the tertiary component of the myenteric plexus, others to the circular muscle. Removal of the myenteric plexus from a short length of intestine caused a loss of nerve fibres from the circular muscle beneath the site of operation and a decrease in fibre density in the circular muscle that extended anally from the lesion for about 1 mm. The nerve lesions caused no significant changes in the tertiary plexus. It is concluded that GABA is contained in motor neurons supplying the longitudinal and circular muscle, and that the neurons supplying the circular muscle may be inhibitory.

Animals↗
PubMed1989

The relationship between gastrin cells and bombesin-like immunoreactive nerve fibres in the gastric antral mucosa of guinea-pig, rat, dog and man.

The relationship between bombesin-like immunoreactive (bombesin-LI) nerve fibres and gastrin-LI G-cells was examined in gastric antral mucosa from guinea-pig, rat, dog and man using a double-labelling fluorescence immunohistochemical technique. The greatest density of bombesin-LI nerve fibres was found within the basal mucosa in all species and the density of innervation decreased towards the luminal surface. Most G-cells were in a band occupying approximately the middle third of the mucosa. The proportion of G-cells found within a distance of 2 microns from bombesin-LI nerve fibres was low in all species (6% in the guinea-pig, 22% in the rat, 14% in the dog, and 9% in the human). It is proposed that the neuropeptide released from bombesin-LI antral mucosal nerve fibres traverses distances of greater than several microns to reach the target G-cells. This may be achieved by passage through the mucosal microcirculation.

Adult↗
PubMed1989

Projections of neurons with neuromedin U-like immunoreactivity in the small intestine of the guinea-pig.

Neuromedin U immunoreactivity was located histochemically in the guinea-pig small intestine. Projections of immunoreactive neurons were determined by analysing patterns of degeneration following nerve lesions. The co-localization of neuromedin U immunoreactivity with immunoreactivity for substance P, neuropeptide Y, vasoactive intestinal peptide and calbindin was also investigated. Neuromedin U immunoreactivity was found in nerve cells in the myenteric and submucous plexuses and in nerve fibres in these ganglionated plexuses, around submucous arterioles and in the mucosa. Reactive fibres did not supply the muscle layers. Most reactive nerve cells in the myenteric ganglia had Dogiel type-II morphology and in many there was co-localization of calbindin, although some Dogiel type-II neuromedin U neurons were calbindin negative. Lesion studies suggest that these myenteric neurons project circumferentially to local myenteric ganglia. Projections from myenteric neurons also run anally in the myenteric plexus, while other projections extend to submucous ganglia, and still further projections run from the intestine to provide terminals in the coeliac ganglia. In the submucous ganglia neuromedin U was co-localized in three populations of nerve cells: (i) those with vasoactive intestinal peptide immunoreactivity, (ii) neurons containing neuropeptide Y, and (iii) neurons containing substance P. Each of these populations sends nerve fibres to the mucosa. Neuromedin U immunoreactivity is thus located in a variety of neurons serving different functions in the intestine and therefore probably does not have a single role in intestinal physiology.

Animals↗
PubMed1989

Calbindin 28 kDa in endocrine cells of known or putative calcium-regulating function. Thyro-parathyroid C cells, gastric ECL cells, intestinal secretin and enteroglucagon cells, pancreatic glucagon, insulin and PP cells, adrenal medullary NA cells and some pituitary (TSH?) cells.

The distribution of calbindin in some endocrine glands (thyroid, parathyroid, ultimobranchial body, pituitary and adrenals) and in the diffuse endocrine cells of the gut and pancreas has been investigated immunohistochemically using an antiserum raised against the 28 kDa calbindin from chicken duodenum. The identity of calbindin-immunoreactive cells in a number of avian and mammalian species was ascertained by comparison with hormone-reactive cells in consecutive sections or by double immunostaining of the same section with both calbindin and hormone antibodies. Calcitonin-producing C cells of the mammalian and avian thyroid, parathyroid or ultimobranchial body, PP, glucagon and insulin cells of the mammalian and avian pancreas, enteroglucagon cells of the avian intestine, secretin cells of the mammalian duodenum, histamine-producing ECL cells of the mammalian stomach, as well as noradrenaline-producing cells of the adrenal medulla and some (TSH?) cells of the adenohypophysis were among the calbindin-immunoreactive cells. Although some species variability has been observed in the intensity and distribution of the immunoreactivity, especially in the pancreas and the gut, a role for calbindin in the mechanisms of calcium-mediated endocrine cell stimulation or of intracellular and extracellular calcium homeostasis is suggested.

Animals↗
PubMed1989

Calbindin immunoreactivity is a characteristic of enterochromaffin-like cells (ECL cells) of the human stomach.

Immunoreactivity for the calcium binding protein, calbindin D28k has been localized in enterochromaffin-like (ECL) cells of the human stomach. The reactivity was observed with three different antisera, raised against bovine brain, primate brain, and chicken intestinal calbindin. The ECL cells were closed endocrine cells located at the bases of the oxyntic glands. They were not found in other regions of the stomach. No other gastric endocrine cells were reactive with these antisera.

Adult↗
PubMed1989

Evidence for two types of 5-hydroxytryptamine receptor on secretomotor neurons of the guinea-pig ileum.

Flat sheet preparations of the mucosa plus submucosa from the guinea-pig ileum were placed in Ussing chambers so that short circuit current (Isc), an index of electrolyte movement across the mucosa, could be measured. In these preparations, 5-hydroxytryptamine (5-HT) increases Isc indirectly by stimulating both cholinergic and non-cholinergic secretomotor neurons. The 5-HT3 receptor antagonist, ICS 205-930 (10(-13)-10(-5 M), substantially depressed the secretory response due to 5-HT (10(-6) M), but not that produced by direct activation of muscarinic receptors on the mucosal epithelium with carbachol (10(-6) M), or by stimulation of secretomotor neurons with substance P (10(-8) M) or 1,1-dimethyl-4-phenylpiperazinium (10(-5)M). The residual response to 5-HT, after the addition of a maximally effective concentration of ICS 205-930 (10(-6) M), was further reduced by hyoscine (10(-7) M). When that part of the 5-HT response attributable to the release of acetylcholine was blocked by hyoscine (10(-7) M), ICS 205-930 did not further modify the response to 5-HT. The hyoscine-resistant component was, however, substantially depressed by tetrodotoxin (3.5 x 10(-7) M). The response remaining after ICS 205-930 and hyoscine was not affected by methysergide (2 x 10(-5) M) or cyproheptadine (10(-7) M). We conclude that there are ICS 205-930 sensitive 5-HT receptors on cholinergic secretomotor neurons, and ICS 205-930, methysergide, and cyproheptadine insensitive 5-HT receptors on non-cholinergic secretomotor neurons.

Animals↗
PubMed1989

Migration of the myoelectric complex after interruption of the myenteric plexus: intestinal transection and regeneration of enteric nerves in the guinea pig.

The effects of surgical interruption of the myenteric plexus (myectomy), extrinsic denervation of a length of small intestine, or transection and reanastomosis of the intestinal wall on migration of phase III of the migrating myoelectric complex was studied in guinea pigs. In addition, the recovery of phase III migration and the regrowth of intestinal nerves and muscle across the reanastomosis was studied at various times up to 60 days after surgery. At 6-9 days after surgery, phase III did not migrate past the myectomy during 50%-60% of recorded migrating myoelectric complexes and transection and reanastomosis of the intestinal wall blocked aboral progression of phase III in 90% of cases. Extrinsic denervation did not alter phase III migration through the denervated segment. Phase III migration past the reanastomosis recovered with time after surgery; 80% recovery occurred by 60 days after surgery. Immunoreactivities for vasoactive intestinal peptide, gastrin-releasing peptide, and somatostatin were used as markers for intestinal nerves that were cut by transaction. Immunoreactivities for vasoactive intestinal peptide and gastrin-releasing peptide are contained in myenteric neurons that project in an oral to anal direction to other myenteric ganglia and to the circular muscle. Immunoreactivity for somatostatin is contained in nerve fibers projecting aborally to other myenteric ganglia. At 7-15 days after surgery, there were accumulations of immunoreactivities for vasoactive intestinal peptide, gastrin-releasing peptide, and somatostatin in nerve fibers on the oral side of the reanastomosis, but nerve fibers containing these peptides were not observed in myenteric ganglia or circular muscle close to the anal edge. At 23-28 days, immunoreactivities for vasoactive intestinal peptide, gastrin-releasing peptide, and somatostatin nerve fibers were traced across the reanastomosis and nerve terminals were detected in ganglia and muscle close to the lesion on the anal side. Nerve fibers traversed the lesion in all cases at 57-60 days and vasoactive intestinal peptide-, gastrin-releasing peptide-, and somatostatin-immunoreactive nerve terminals were detected in the first two to three rows of myenteric ganglia on the anal side. Regrowth of intestinal muscle followed a similar time-course to that observed for nerves. These data suggest that interruption of the myenteric plexus alone does not completely block phase III migration. In addition, recovery of phase III migration past a reanastomosis is associated with a restoration of both nervous and mechanical connections.

Animals↗
PubMed1989

Distribution of enteric nerve cells that project from the small intestine to the coeliac ganglion in the guinea-pig.

The retrograde tracing agent, Fast blue, was injected into the coeliac ganglia of guinea-pigs and 4-7 days later, nerve cell bodies containing this dye were examined in the small intestine. The cell bodies were found in the ganglia of the myenteric plexus but not in submucous ganglia. The labeled cell bodies were large, on average 42 by 19 microns when viewed in whole mounts, with 4-9 fine processes. The cells increased in frequency anally along the small intestine; the number of neurons per unit length of gut in the distal ileum was more than double that near the duodeno-jejunal flexure. At all points along the intestine the nerve cells were more numerous near the mesenteric attachment than opposite this attachment. About half of the neurons showed immunoreactivity for VIP. It is deduced that the neurons that project from the intestine to the coeliac ganglion are likely to be second-order neurons in the afferent limbs of intestino-visceral reflex pathways.

Amidines↗
PubMed1989

An electrophysiological comparison of substance P-immunoreactive neurons with other neurons in the guinea-pig submucous plexus.

Intracellular microelectrodes containing the dye Lucifer yellow CH were used to record from nerve cells of ganglia in isolated preparations of submucosa from the guinea-pig small intestine. The electrophysiological properties of the neurons were investigated by passing intracellular current pulses and by stimulating nerve strands that connect with the ganglia. Following each electrophysiological investigation, the fluorescent dye was injected into the neuron by passing hyperpolarizing currents through the electrode. The preparations were fixed and processed for substance P (SP) immunohistochemistry. When impaled neurons were not immunoreactive for SP the preparations were processed first for vasoactive intestinal peptide immunoreactivity and then for neuropeptide Y immunoreactivity. Data from neurons reactive for either of these peptides were pooled for comparison with the data from SP-immunoreactive neurons. Nerve cells that were immunoreactive for SP were usually multipolar, had broad action potentials (half width 2.6 ms compared with 1.5 ms for other submucous neurons) and lower input resistances than other submucous neurons. Only a minority (6 of 18) had demonstrable fast excitatory synaptic inputs. When such excitatory synaptic inputs were observed, these did not initiate action potentials. Thus, the SP-immunoreactive neurons were readily distinguishable from other submucous neurons. It is concluded that these neurons are likely to be sensory.

Animals↗