Reinnervation of transplanted mouse pancreatic islets.
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Acetylcholinesterase↗
Biomedical subjects
F Sundler
Publications and source records attributed to F Sundler.
VIP-containing nerve fibres in the submandibular gland of the dog and protein secretion in vitro in response to VIP.
Previously, administration of VIP has been shown to elicit no flow of saliva from the submandibular gland of the dog. However, in the present study we found VIP to cause release of protein in vitro from canine submandibular gland tissue. Furthermore, VIP-containing nerve fibres were demonstrated in large numbers in association with acini. Thus, VIP may be involved in the nervous regulation of salivary protein secretion in the dog.
Animals↗
Gastrin-releasing peptide: neuronal distribution and spatial relation to endocrine cells in the human upper gut.
By using immunocytochemical techniques, we have studied the distribution of gastrin releasing peptide (GRP)-containing neurons as well as the spatial relationship between these neurons and the endocrine cells in the human stomach and duodenum. Moderate numbers of immunoreactive fibers were distributed in the smooth muscle and submucosa of the stomach; they were more rare in the duodenal wall. Numerous GRP-containing nerve fibers were found in the oxyntic mucosa, the antral mucosa harboured only few GRP immunoreactive nerve fibers. The mucosa of the proximal duodenum was found to be virtually devoid of such fibers. Only occasionally did we observe signs of a direct contact between GRP-containing nerve fibers and gastrin and somatostatin cells in the antral mucosa. In the oxyntic mucosa GRP-containing nerve fibers sometimes seemed to contact endocrine cells, including somatostatin cells as well as individual parietal cells. In conclusion, although GRP-containing nerve fibers were quite numerous in the wall of the human upper gastro-intestinal (GI)-tract, we observed a lack of intimate spatial relationship between these fibers and endocrine cells in the antral mucosa, suggesting additive mechanisms to a direct innervation of gastrin cells and somatostatin cells by GRP nerve fibers explaining the physiological effects on hormonal release.
Adult↗
Evidence that gastrin enhances 45Ca uptake into bone through release of a gastric hormone.
An acute challenge with gastrin-17 enhanced the uptake of 45Ca into sternum and several long bones in rats by about 10-30%; gastrectomy prevented this effect. Long-term treatment with (Leu15)-gastrin-17 (continuous infusion via osmotic minipumps for 4 weeks) enhanced the uptake of 45Ca into bone (examplified by radius and sternum) by 18-26% (tested on the last day of the infusion). Surgical removal of the acid-producing part of the stomach (fundectomy) or treatment with the anti-ulcer drugs, ranitidine (a histamine H2-receptor antagonist administered by continuous infusion) or omeprazole (an H+/K(+)-ATPase inhibitor administered daily by gastric tube for 4 weeks), induced sustained hypergastrinemia (through loss of acid feedback inhibition of gastrin release). The ranitidine- and omeprazole-evoked hypergastrinemia was associated with 32-62% enhancement of bone 45Ca uptake but the hypergastrinemia of fundectomized rats was not. Gastrectomy abolished the effect of omeprazole. We suggest that exogenous and endogenous gastrin influences calcium uptake into bone indirectly by releasing a calciotropic hormone (gastrocalcin) from the acid-producing part of the stomach. The bone ash weight was reduced by gastrectomy or fundectomy (4 weeks), but neither ranitidine nor omeprazole-evoked hypergastrinemia (4 weeks) raised the bone ash weight. The stimulated calcium uptake into bone of hypergastrinemic rats treated with ranitidine or omeprazole was associated with a 22-32% increase in the density of osteoclasts in the tibia. This finding is in line with the hypothesis that long-lasting hypergastrocalcinemia produces accelerated turn-over of bone rather than increased bone calcium content.
Animals↗
Peptide-containing nerve fibers in the circumvallate papillae.
The occurrence and distribution of an array of neuropeptides and dopamine-beta-hydroxylase in the circumvallate papillae of monkey, pig, cow, ferret, cat, rat and mouse was studied by immunocytochemistry. The animals were chosen to represent species with different diets. Substance P/neurokinin A- and calcitonin gene-related peptide-containing fibers were numerous in the circumvallate papillae of all animals examined, with the highest frequency in monkey, pig, cow, rat and mouse; in ferret and cat moderate numbers were detected. Vasoactive intestinal peptide/peptide histidine isoleucine amide-containing fibers were numerous in the circumvallate papillae of pig, while they were moderate in number in monkey, ferret and mouse. Neuropeptide Y-containing fibers were few to moderate in number in the circumvallate papillae of all species. Galanin-containing fibers were numerous in the pig circumvallate papillae, while only a few fibers could be detected in monkey, cow, cat, rat and mouse. Somatostatin-containing fibers were seen only in the cat circumvallate papillae, gastrin-releasing peptide-containing fibers in the cow and cat, cholecystokinin/gastrin-containing fibers in the pig and cow. Dopamine-beta-hydroxylase-containing fibers were detected in all animals studied. They were few to moderate in number in the circumvallate papillae. There was no obvious link between the peptidergic innervation pattern and the food habits.
Animals↗
Intestinal endocrine cells in Hirschsprung's disease. No reduction in density in aganglionic compared with ganglionic segment.
The aganglionic intestine in Hirschsprung's disease displays a severe neuronal derangement. The changes are particularly evident in the muscular innervation. In the gut the endocrine cells are among the cells known to be influenced by neurons. We have, therefore, examined the endocrine cells in ganglionic and aganglionic intestine using immunocytochemistry and immunochemistry. The endocrine cells were studied using antibodies against the neuroendocrine marker chromogranin A, the amine serotonin and the hormonal peptides somatostatin, glucagon/glicentin and peptide YY (PYY), thus covering virtually all endocrine cell types known to occur in this region. The PYY concentration in the mucosal layer was measured by radioimmunoassay. In ganglionic as well as in aganglionic intestine large populations of cells storing chromogranin A, serotonin, glucagon and PYY and a smaller population of somatostatin cells were seen. There was an increase in the density of these cells in the aganglionic intestine compared with ganglionic. The data indicate that the endocrine cell populations in the intestinal wall can be maintained despite severe derangements of the nerve supply.
Cell Count↗
Galanin is co-localized with noradrenaline and neuropeptide Y in dog pancreas and celiac ganglion.
To visualize the localization and potential co-localization of noradrenaline and the putative pancreatic sympathetic neurotransmitters, galanin and neuropeptide Y (NPY), immunofluorescent staining for galanin, NPY and tyrosine hydroxylase (TH) was performed on sections of canine pancreas and celiac ganglion. In the pancreas, galanin-immuno-fluorescent nerve fibers were confirmed as densely and preferentially innervating the islets, whereas numerous NPY-positive nerve fibers were found in the exocrine parenchyma, the surrounding of the blood vessels and within the islets. Double-staining for the peptides and TH indicated that most galanin-positive nerve fibers were adrenergic, most NPY-positive nerve fibers were adrenergic, and many islet nerves contained both galanin and NPY, although some galanin-positive nerve fibers appeared to lack NPY. In the celiac ganglion, virtually all cell bodies were positive for both galanin and TH; a large subpopulation of these cells were also positive for NPY. Radioimmunoassay (RIA) of galanin in extracts of dog celiac ganglion revealed a very high content (256 +/- 33 pmol/g wet weight) of galanin-like immunoreactivity (GLIR), consistent with the dense staining observed. This GLIR behaved in a similar manner to synthetic porcine galanin in the RIA. In addition, the majority of the GLIR in ganglion extracts co-eluted with the synthetic peptide upon gel filtration, although a minor peak of a larger apparent molecular weight was also observed, observations consistent with the presence of a precursor peptide. These findings suggest that galanin is a sympathetic post-ganglionic neurotransmitter in the canine endocrine pancreas and that NPY might serve a similar function.
Animals↗
Carcinoid granule extract contains antigenic determinants common to peptide hormone-producing cells and endocrine tumours.
Some soluble proteins, such as the chromogranins, are found in nearly all peptide hormone-producing cells. Little is known about their functional role, although they may act as enzymes or represent structural proteins. In the present study we have isolated granules from an ileal carcinoid tumour and raised antibodies to protein constituents within them. The antiserum proved to be useful for the immunohistochemical demonstration of peptide hormone-producing endocrine tumours in general and for the demonstration of most peptide hormone-producing cells.
Animals↗
Histology of gastric biopsies from peptic ulcer patients before and after short-term treatment with omeprazole or H2-receptor antagonists.
Sixty patients with duodenal or prepyloric ulcers were given omeprazole (30 or 40 mg o.m.; average period of treatment: 2.9 weeks) or histamine H2-receptor antagonists (cimetidine 400 mg b.i.d. or ranitidine 150 mg b.i.d.; average period of treatment; 3.5 weeks) for a single period ranging between 2 and 6 weeks. At the end of the treatment period fasting plasma gastrin levels were moderately increased in both groups in comparison with the pretreatment values. Endoscopic biopsies were taken from the oxyntic mucosa at the beginning and at the end of the treatment period. Light microscopy of the biopsies was aimed particularly at determining the number of endocrine cells. In addition, the mucosal thickness and the volume densities of the parietal cells, the lamina propria and the gland lumina were measured. There were no significant differences in the endocrine or parietal cell populations, between biopsies taken from the patients before and after treatment with omeprazole or histamine H2-receptor antagonists. The mucosal thickness and the densities of the lamina propria and of the gland lumina remained unaffected by the treatment.
Adult↗
Neuropeptide-containing nerve fibers in the pharynx of the rabbit.
The distribution of peptide-containing nerve fibers in the pharyngeal region of rabbits was studied by immunocytochemistry. Neuropeptide Y (NPY)-containing fibers were numerous around blood vessels and moderate in number among bundles of striated muscle fibers. A few NPY-containing fibers were seen around seromucous glands and beneath the epithelium. Nerve fibers containing vasoactive intestinal peptide (VIP) were numerous around seromucous glands and moderate in number around blood vessels, bundles of muscle, and in the subepithelial layer. A few nerve fibers containing substance P (SP) were seen around blood vessels, seromucous glands, among bundles of muscle, and in the subepithelial layer. Nerve fibers containing calcitonin gene-related peptide (CGRP) were numerous. They were distributed close to blood vessels, among bundles of muscle, in the subepithelial layer, and within the epithelium. A conspicuous finding was the occurrence of CGRP within motor end plates of striated muscle.
Animals↗
Gastrin stimulates the self-replication rate of enterochromaffinlike cells in the rat stomach. Effects of omeprazole, ranitidine, and gastrin-17 in intact and antrectomized rats.
The enterochromaffinlike cells in the rat stomach are rich in histamine and are thought to be under the influence of gastrin. The effect of sustained endogenous and exogenous hypergastrinemia on the activity and proliferation rate of the enterochromaffinlike cells was studied by determining the histidine decarboxylase activity and histamine concentration and by combining histamine immunocytochemistry and autoradiography after in vivo labeling with [3H]thymidine. The proliferation rate of the stem cells in the oxyntic mucosal progenitor zone was also studied. Exogenous hypergastrinemia was induced by infusion of rat gastrin-17 (60 nmol.kg-1.day-1). Endogenous hypergastrinemia was induced by inhibition of gastric acid secretion with omeprazole (80 mumol.kg-1.day-1) or ranitidine (1200 mumol.kg-1.day-1). The effect of omeprazole was also studied in antrectomized rats. In intact rats, all treatments resulted in elevated plasma gastrin levels and were accompanied by an increase in the histidine decarboxylase activity and the histamine content of the oxyntic mucosa. This resulted in an increase in the enterochromaffinlike cell proliferation rate, leading to enterochromaffinlike cell hyperplasia. The number of labeled stem cells was increased, but this effect was not as pronounced as in the enterochromaffinlike cells. In antrectomized rats, the inhibition of acid secretion by omeprazole did not result in elevated plasma gastrin or in an increase in the activity or number of enterochromaffinlike cells, indicating that omeprazole per se had no effect on these cells. These data support the view that gastrin stimulates the proliferation rate of both enterochromaffinlike cells and stem cells. Gastrin also stimulates the activity of the enterochromaffinlike cells.
Animals↗
Enhanced hyperplasia of gastric enterochromaffinlike cells in response to omeprazole-evoked hypergastrinemia in rats with portacaval shunts. An immunocytochemical and chemical study.
The histamine-storing enterochromaffinlike cells, which are numerous in the oxyntic mucosa of the rat stomach, are known to proliferate in response to long-lasting hypergastrinaemia. In addition, portacaval shunting, which is not associated with elevated serum gastrin, causes an increase in enterochromaffinlike cell density. The present study shows that the combination of portacaval shunting and omeprazole-evoked, long-lasting hypergastrinemia results in enhanced enterochromaffinlike cell hyperplasia despite the fact that the hypergastrinemia was not significantly greater than in intact omeprazole-treated rats. The mechanism behind the enhanced response to gastrin of the enterochromaffinlike cells in rats with portacaval shunts is unknown. When results from untreated and omeprazole-treated rats were plotted, there was a linear correlation between the serum gastrin concentration and the enterochromaffinlike cell density in both sham-operated rats and rats with portacaval shunts. We conclude that gastrin plays a role in the development of enterochromaffinlike cell hyperplasia following omeprazole treatment in rats with portacaval shunts but that other as yet unidentified agents may also promote the response.
Animals↗
Trophic effects of continuous infusion of [Leu15]-gastrin-17 in the rat.
This report describes the trophic effects of exogenous gastrin on the digestive tract and pancreas and the effect on the density of enterochromaffinlike cells in the oxyntic mucosa of the stomach. Female rats were given 1.2 or 2.4 nmol/kg.h of synthetic human [Leu15]-gastrin-17 for 28 days (via osmotic minipumps implanted subcutaneously). As a result, measurable plasma gastrin increased from about 230 pg/ml in the controls to about 500 and 800 pg/ml in the low- and high-dose groups, respectively. The trophic effects of gastrin were reflected in increased stomach weight and oxyntic mucosal mass. Gastrin also increased the enterochromaffinlike cell density and associated parameters (histamine concentration and histidine decarboxylase activity) but was without demonstrable effects on other parts of the digestive tract and pancreas. The results show that continuous infusion of exogenous gastrin for 28 days induces trophic changes similar to those seen after a period of hypergastrinemia induced by treatment with effective inhibitors of acid secretion.
Animals↗
Peptide-containing neurons projecting to the vocal cords of the rat: retrograde tracing and immunocytochemistry.
The distribution and origin of neuropeptide Y-, vasoactive intestinal peptide- and calcitonin gene-related peptide-containing nerve fibers and adrenergic (dopamine-beta-hydroxylase-containing) fibers in the rat larynx were studied by retrograde tracing and selective denervations in combination with immunocytochemistry. An injection of the retrograde tracer True Blue to the right vocal cord resulted in the appearance of labelled nerve cell bodies in the ipsi- and contralateral superior cervical and stellate ganglia, the thyroid ganglia, the jugular-nodose ganglionic complexes, in the ipsilateral trigeminal and dorsal root ganglia at levels C2 and C3 and in local tracheal ganglia. Judging from the number of labelled nerve cell bodies, the jugular-nodose ganglionic complexes, dorsal root ganglia and superior cervical ganglia provide the greater part of the vocal cord innervation. Most of the True Blue-labelled nerve cell bodies in the superior cervical and stellate ganglia contained neuropeptide Y. In the thyroid ganglia the majority of labelled nerve cell bodies contained vasoactive intestinal peptide. In the jugular-nodose ganglionic complex and the dorsal root ganglia the majority of the labelled nerve cell bodies stored calcitonin gene-related peptide. Retrograde tracing and denervation studies revealed that all noradrenaline- and the majority of neuropeptide Y-containing nerve fibers emanate from the superior cervical and stellate ganglia. A minor population of neuropeptide Y-containing nerve fibers originate in local tracheal ganglia. The vasoactive intestinal peptide-containing nerve fibers originate in the thyroid ganglion and local tracheal ganglia, whereas calcitonin gene-related peptide-containing nerve fibres emanate from the dorsal root ganglia (C2-C3), the trigeminal ganglia and the jugular-nodose ganglia.
Animals↗
Is the reduction of VIP the clue to the pathophysiology of Hirschsprung's disease?
The reduction of vasoactive intestinal peptide-(VIP) containing nerve fibres in the aganglionic segment in Hirschsprung's disease is thought to contribute to the sustained contraction of this intestinal segment. In order to study the significance of VIP in the pathogenesis of Hirschsprung's disease we used immunohistochemistry to evaluate the reduction of VIP-immunoreactive nerve fibres in aganglionic intestine compared to the ganglionic one. The VIP nerve fiber density was compared with the type of onset of disease (e.g. neonatal ileus or obstipation) and with the length of the aganglionic segment. No statistically significant correlation between these factors could be registered. This indicates a high complexity of the neuronal derangement in aganglionic intestine and that the degree of VIP deficiency alone does not correlate with the severity of the disease.
Colon↗
Localization and peptide content of endocrine pancreatic tumors.
Endocrine pancreatic tumors contain and frequently secret neurohormonal peptides. This phenomenon can be used as a diagnostic and classifying tool. This study analyzes 31 patients operated on because of an endocrine pancreatic tumor, including the diagnostic procedures and the localization methods. In 15 insulinoma cases only 6 patients had a positive arteriography, while all 11 selective pancreatic vein samplings were positive. The immunoreactivity showed that, besides insulin, most tumors also contained other peptides. Of four gastrinoma cases the arteriography was positive in three, but the selective vein sampling localized the tumor in all. The tumor's content of peptides showed mixed patterns. In the four glucagonomas, the arteriography was positive in all and the venous sampling performed in three of the cases also was positive. In five pancreatic polypeptide-containing tumors (PP-omas) the arteriography was positive in four and sampling performed in two was positive in both. In the PP-omas the peptide pattern showed that these tumors frequently contain several peptides. We used selective pancreatic vein sampling in 21 cases with positive result in all. In the cases in which arteriography was negative, the sampling results helped the surgeon to find the tumor. The peptide pattern in the tumors varied greatly and most tumors were multihormonal.
Adult↗
Proposed mechanism of induction of gastric carcinoids: the gastrin hypothesis.
Novel, powerful and long-acting inhibitors of gastric acid secretion include second generation H2-blockers and so-called proton pump inhibitors, such as omeprazole. Gastric carcinoids were found to develop in experimental animals as a consequence of continuous long-term administration of several of these highly effective anti secretory drugs. This unwanted side effect is now thought to reflect the fact (1) that pharmacological blockade of acid secretion results in hypergastrinaemia, and (2) that long-standing hypergastrinaemia gives rise to hyperplasia of certain endocrine cells, the so-called ECL cells, in the gastric mucosa. The carcinoids that develop in the rat stomach after lifelong treatment with antisecretagogues arise from the ECL cells. The proposed sequence of events is acid blockade--hypergastrinaemia--ECL cell hyperplasia--carcinoid. This concept, referred to as the gastrin hypothesis, maintains that the ECL cell hyperplasia (and possibly the carcinoids) is a consequence of long-term continuous hypergastrinaemia.
Animals↗
Muscarinic supersensitivity in the rat urinary bladder after capsaicin pretreatment.
The effects of capsaicin on urinary bladder function have been investigated in adult rats. Ten days after capsaicin treatment immunocytochemical investigations showed a nearly complete disappearance of substance P (SP) and calcitonin gene-related peptide (CGRP) in all parts of the bladder. Recordings of micturition patterns and cytometrical investigations in conscious animals revealed no functional effects of capsaicin treatment. In-vitro experiments showed that the contractile response to substance P was similar before and after capsaicin treatment and CGRP exerted no contractile effects on the urinary bladder in either group of rats. The concentration-response curve to carbachol as well as the frequency-response curve to electrical stimulation were significantly shifted to the left in bladder muscle after capsaicin treatment. However, the maximal responses were similar in control and capsaicin-treated bladders. In the presence of scopolamine the maximal response to electrical stimulation was clearly lower in bladders subjected to capsaicin treatment than in controls. In conclusion, depletion of substance P and CGRP in the rat urinary bladder by capsaicin induced no supersensitivity to these peptides. However, the increased sensitivity to carbachol and to electrical stimulation seen after capsaicin treatment indicates the development of a supersensitivity to muscarinic receptor stimulation. Despite this supersensitivity in vitro no functional effects of capsaicin treatment were found in vivo.
Animals↗