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F Sundler

Publications and source records attributed to F Sundler.

At least 217 records · Page 12Linked to original sources
PubMed1991

Immunocytochemical localisation of pancreastatin and chromogranin A in porcine neuroendocrine tissues.

Pancreastatin is a 49 amino acid peptide with a C-terminal glycine amide originally isolated from porcine pancreas. In the present study the cellular localisation of pancreastatin in porcine neuroendocrine tissue was examined immunocytochemically using an antiserum raised against porcine pancreastatin (33-49) that does not cross-react with porcine chromogranin A. In order to study the possible precursor-product relationship between chromogranin A and pancreastatin the cellular localisation of both peptides was examined in peripheral tissues using simultaneous double immunostaining. The pancreastatin antiserum immunostained cells and nerve fibers throughout the neuroendocrine system. In most of the examined tissues we found colocalisation of pancreastatin and chromogranin A immunostaining. These results support the precursor-product concept for chromogranin A and pancreastatin. However, in the gastrointestinal tract and the adenohypophysis a minor population of the endocrine cells exhibited immunostaining with only one of the two antibodies. This discrepancy between immunostaining with pancreastatin antiserum and monoclonal chromogranin A antibody could be due to absence of, or extensive, processing of chromogranin A in certain cell populations.

Animals↗
PubMed1991

Peptide-containing nerve fibers in the fungiform papillae of pigs and rats.

The occurrence and distribution of an array of neuropeptides and dopamine-beta-hydroxylase in the fungiform papillae of pigs and rats were studied by immunocytochemistry. Structural differences between the fungiform papillae of the two species were correlated to differences in the occurrence and distribution of neuropeptides. Calcitonin gene-related peptide-, substance P- and neurokinin A-containing fibers were numerous in the fungiform papillae of both species, although their distribution within the papilla differed. In the pig, the majority of these fibers ended within the taste buds, while in the rat numerous fibers also penetrated the adjacent epithelium. Galanin- and bombesin-immunoreactive nerve fibers could not be detected in the rat fungiform papillae, while in the pig many, but not all, of the fungiform papillae contained bombesin- and galanin-positive nerve fibers. Vasoactive intestinal peptide- and peptide histidine isoleucine-immunoreactive fibers occurred in the fungiform papillae of both species. A few neuropeptide Y-containing fibers and dopamine-beta-hydroxylase-positive (presumably adrenergic) fibers could be observed in the porcine papillae only.

Animals↗
PubMed1991

Presence of galanin in human pancreatic nerves and inhibition of insulin secretion from isolated human islets.

In several animal species, galanin occurs in pancreatic nerves and inhibits insulin secretion. However, the presence and action of galanin in the human pancreas have not been established. Therefore, we examined the presence and nature of human pancreatic galanin-like immunoreactive material (GLIR) and the effects of galanin on glucose-stimulated insulin secretion from isolated human islets. Immunofluorescent staining of human pancreas revealed GLIR in fine varicose fibers in both islets and exocrine parenchyma. Furthermore, acid extracts of pancreas (n = 3) and isolated islets (n = 3) contained 0.17 +/- 0.06 and 0.23 +/- 0.11 pmol GLIR/mg protein. Human pancreatic GLIR coeluted with synthetic porcine galanin from Sephadex G-50. Moreover, synthetic porcine galanin inhibited glucose-stimulated insulin secretion from collagenase-isolated human islets at dose rates greater than 10(-8) M. Thus, (1) human pancreas is innervated by galanin-containing nerves, (2) human pancreatic GLIR is of similar size as synthetic porcine galanin, and (3) porcine galanin inhibits glucose-stimulated insulin secretion from human islets. Therefore, galanin could be an important local regulator of insulin secretion in man.

Animals↗
PubMed1991

Galanin-immunoreactive nerves in the mouse and rat pancreas.

Galanin-containing nerve fibers have previously been observed in the human, dog, and pig pancreas. Whether the mouse and rat pancreas also contain galanin nerve fibers has been a matter of debate. Therefore, we examined the distribution of galanin in the mouse and the rat pancreas. Further, the possible localization of galanin to adrenergic nerves was studied using sequential immunostaining for galanin and tyrosine hydroxylase (TH). In the mouse pancreas, numerous galanin-immunoreactive (GIR) nerve fibers occurred around blood vessels. They were less numerous in the exocrine parenchyma and in association with the islets. In contrast, in the rat pancreas, only a few GIR nerves were found. They were located around blood vessels and scattered in the exocrine parenchyma. Occasionally, GIR nerves were also observed in the islets. There was a dense distribution of TH-immunoreactive fibers in both the mouse and the rat pancreas. Sequential immunostaining revealed co-localization of galanin and TH immunoreactivity in nerve fibers in both the mouse and the rat pancreas. Following chemical sympathectomy using 6-hydroxydopamine (6-OHDA), not all GIR nerves disappeared. In the mouse pancreas a remaining population of galanin nerves was found around blood vessels, and occasionally in the islets. In the rat pancreas, a few GIR nerves were seen also after chemical sympathectomy. We conclude that intrapancreatic GIR nerves also occur in the mouse and the rat. These findings suggest that many of the GIR nerves are adrenergic but that non-adrenergic, possibly intrinsic or sensory GIR nerves exist as well in both the mouse and the rat pancreas.

Adrenergic Fibers↗
PubMed1991

Pituitary adenylate cyclase-activating peptide (PACAP), a new vasoactive intestinal peptide (VIP)-like peptide in the respiratory tract.

Pituitary adenylate cyclase-activating peptide (PACAP) is a vasoactive intestinal peptide (VIP)-like peptide recently isolated from ovine hypothalami. Nerve fibers displaying PACAP immunoreactivity were found in the respiratory tract of rats, guinea pigs, ferrets, pigs, sheep and squirrel monkeys. A moderate supply of PACAP-immunoreactive fibers was seen in the nasal mucosa of guinea pigs. Few to moderate numbers of PACAP-containing fibers occurred in the tracheo-bronchial wall of rats, guinea pigs, ferrets, pigs, sheep and squirrel monkeys. The fibers were distributed beneath the epithelium, around blood vessels and seromucous glands, and among bundles of smooth muscle. In the lungs, the immunoreactive fibers were observed close to small bronchioli. A few PACAP-immunoreactive nerve cell bodies were seen in the sphenopalatine and otic ganglia of guinea pigs. Simultaneous double immunostaining of the respiratory tract of sheep and ferrets revealed that all PACAP-containing nerve fibers stored VIP. We suggest that neuronal PACAP may take part in the regulation of smooth muscle tone and glandular secretion.

Animals↗
PubMed1991

Chemical coding of endocrine cells of the airways: presence of helodermin-like peptides.

The epithelium of the airways is rich in endocrine cells containing serotonin and/or a wide variety of regulatory peptides. These cells usually occur in clusters in the lungs but are also found scattered in the larynx and trachea. In the present study, endocrine cells in the airways of mouse, rat, hamster, guinea pig, pig, sheep and squirrel monkey were examined for the presence of serotonin, helodermin-like peptides and other regulatory peptides using immunocytochemistry and radioimmunoassay. In addition, we looked for the protein gene product 9.5 (PGP), which occurs in many peptide hormone-producing endocrine cells in the body. Both clustered and scattered endocrine cells in the airways were found to display coexistence of serotonin and peptides, such as a helodermin-like peptide, calcitonin and calcitonin gene-related peptide (CGRP). The PGP-immunoreactive cells were numerous and included elements containing serotonin and/or regulatory peptides. An additional PGP-immunoreactive endocrine cell population lacked serotonin and regulatory peptides. Helodermin-immunoreactive material was demonstrated in endocrine cells of the airways in the mouse and hamster but not in any of the other species studied. Serotonin was an endocrine cell constituent in all the species studied. Calcitonin and CGRP could be demonstrated by immunocytochemistry in the mouse, rat, and hamster, but not in the guinea pig, sheep, pig and monkey.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

NPY hyperinnervation in Hirschsprung's disease: both adrenergic and nonadrenergic fibers contribute.

In Hirschsprung's disease, the aganglionic bowel is characterized by an absence of ganglion cells and an increased number of adrenergic and presumed cholinergic nerve fibers. In addition, a severe derangement of peptide-containing nerve fibers is encountered including a hyperinnervation of neuropeptide Y (NPY)-containing fibers. Using immunochemical and immunocytochemical methods, we examined the nature of the NPY-containing nerve fibers contributing to the hyperinnervation. The concentration of NPY was markedly increased in the aganglionic segment. Coexistence of NPY, vasoactive intestinal peptide (VIP), and the adrenergic enzyme tyrosine hydroxylase (TH) showed small populations of nerve fibers containing NPY/TH, NPY/VIP, or TH alone in ganglionic intestine. Numerous nerve fibers stored VIP but lacked NPY. These fibers did not contain TH, indicating that all VIP-containing fibers are nonadrenergic. In the aganglionic intestine there was a marked increase in the number of nerve fibers storing NPY/TH and NPY/VIP, whereas the fibers storing VIP alone were reduced in number. A small number of nerve fibers storing NPY alone occurred in the hypertrophic nerve bundles. NPY/VIP-containing nerve fibers were particularly numerous in the mucosa in aganglionic intestine, which may be of interest in the diagnosis of Hirschsprung's disease allowing the use of mucosal biopsy specimens. Thus, the proliferating NPY-containing nerve fibers in the aganglionic intestine seem to comprise three different populations, one adrenergic and two nonadrenergic, one of which contains in addition VIP.

Adrenergic Fibers↗
PubMed1991

Hydrogen peroxide-induced epithelial damage increases terbutaline transport in guinea-pig tracheal wall: implications for drug delivery.

An isolated vagus nerve-tracheal tube preparation from guinea-pig was treated intraluminally with hydrogen peroxide (H2O2) at various concentrations. Exposure to, 100 mmol/L H2O2 for 20 min was chosen for further experiments since it appeared to cause selective damage to the epithelium. Thus the subepithelial layers of the tracheal wall appeared intact as judged by light microscopic examination. The response to nerve stimulation (increase in intratracheal pressure) was attenuated by only about 20%. Terbutaline administration into the tracheal lumen caused a concentration-dependent inhibition of the response to nerve stimulation. In tracheal preparations pretreated with 100 mmol/L H2O2 there was a 20-fold decrease in the EC50 for terbutaline. The EC50 for terbutaline added to the external medium was not changed by the H2O2 pretreatment. The efflux of 3H-terbutaline from the tracheal lumen into the external medium was three times higher in H2O2-treated than in control preparations. It is concluded that in the H2O2-damaged epithelium the absorption of terbutaline is enhanced resulting in a better availability of the drug in the smooth muscle layer after intraluminal administration.

Animals↗
PubMed1991

Plasma exudation as a first line respiratory mucosal defence.

A great variety of provocations of the airway mucosa produce extravasation of plasma from the abundant subepithelial microvessels. A plasma exudate has important actions through its volume, its specific and unspecific binding proteins, its enzyme systems, and its potent peptides (of kinin, complement, coagulation, fibrinolysis and other systems). If allowed to operate on the surface of an intact mucosa the plasma exudate would have important roles in normal airway defence. Recent observations in guinea-pig tracheobronchial airways and in human nasal airways suggest that the mucosal exudation of plasma into the airway lumen is a non-injurious fully reversible process. Threshold exudative responses thus resulted in the appearance of an 'unfiltered' plasma exudate not only in the lamina propria but also on the surface of an undisrupted mucosa. Even after extensive luminal entry of exudate the epithelial lining was intact, as judged by light, fluorescence and electron microscopy. Hence, the epithelial barrier was reversibly permeable when approached from beneath by the plasma exudate. This was a distinct increase in outward permeability, because even during the exudation of plasma the mucosa remained a barrier to luminal solutes. It is possible that the exudate itself, by a slight compressive action on the basolateral aspect of epithelial cells, creates intercellular pathways for its entry into the lumen. Contrary to current beliefs, we propose that plasma exudation should be considered a first line respiratory defence mechanism operating together with other systems of the mucosal surface.

Absorption↗
PubMed1991

Toluene diisocyanate produces an increase in airway tone that outlasts the inflammatory exudation phase.

Toluene diisocyanate (TDI) is a causative agent in occupational asthma. Through an oral catheter TDI, 0.03 microliters, dissolved in 0.02 ml olive oil, was superfused on the tracheobronchial mucosa of anaesthetized guinea-pigs. TDI induced plasma exudation into both airway tissue and lumen (peak effect: 5 hr; duration approximately 17 hr). Light microscopy examinations demonstrated that the epithelium was not disrupted by this process (and that microvessels are abundant just beneath the epithelium). At days 6 and 21 after exposure to TDI PAS-positive cells were increased, but no other histological alterations were found. Also, the occurrence of peptide-containing nerve fibres was not altered by TDI. After TDI-exposure the airway smooth muscle tone was elevated as examined in vitro at base-line and at concentration-response to carbachol. The largest increases in tone were recorded 21 days after exposure to TDI. The abnormally large tone was not associated with an increased thickness of the smooth muscle layer nor was it associated with reduced effects of either beta 2-agonist (terbutaline) or xanthine- (theophylline) relaxants. It is concluded that TDI-induced plasma exudation into guinea-pig airways occurs for 17 hr without disrupting the epithelial lining and without causing major changes in the airway peptidergic innervation. Both the airway tone, and the number of mucous cells, are increased for at least 3 weeks after exposure to TDI.

Airway Resistance↗
PubMed1991

Immunoreactive delta sleep-inducing peptide in the rat hypothalamus, pituitary and adrenal gland: effects of adrenalectomy.

Immunoreactive (IR) delta sleep-inducing peptide (DSIP) was examined by immunocytochemistry in the rat pituitary and adrenal gland and found to be colocalized with IR thyroid-stimulating hormone in the pituitary and with noradrenaline in the adrenal medulla. IR-DSIP was also detectable in nerve fibers in the posterior pituitary. By radioimmunoassay, IR-DSIP was quantified in plasma and tissue extracts after uni- or bilateral adrenalectomy. Significantly elevated plasma levels of IR-DSIP were measured 5 days after bilateral adrenalectomy (p less than 0.001). IR-DSIP was increased (p less than 0.05) in pituitary extracts from bilaterally adrenalectomized rats after 5 days, but not after 14 or 28 days. Sham- and unoperated animals did not significantly differ in plasma or tissue concentration of IR-DSIP. High-performance liquid chromatography of C18 SEP-PAK purified hypothalamus extracts revealed a single peak of IR-DSIP material of lower hydrophobicity than synthetic DSIP. The elevated concentration of IR-DSIP in the rat pituitary and plasma after bilateral adrenalectomy is consistent with the previously suggested role of DSIP to influence the activity of the hypothalamic-pituitary-adrenal axis.

Adrenal Glands↗
PubMed1991

The effect of omeprazole-induced hypergastrinemia on the oxyntic mucosa of mastomys.

Mastomys is a rodent with a high incidence of spontaneous carcinoids in the acid-producing part of the stomach. The present study was conducted to examine whether hypergastrinemia could promote tumor formation in this species. Mastomys, 4 months of age, were treated for 5 months with omeprazole subcutaneously, 100 mumol/kg body weight daily, and compared with mastomys given the vehicle only. The plasma gastrin concentration and the number of antral gastrin cells were increased in the omeprazole-treated group. The hypergastrinemia was associated with elevated histidine decarboxylase activity and histamine content in the oxyntic mucosa and with a trophic effect on the oxyntic mucosa and the enterochromaffin-like cells. However, no carcinoid tumors were observed, possibly because the strain of mastomys studied does not produce carcinoids spontaneously.

Animals↗
PubMed1991

Histamine-producing cells in the stomach and their role in the regulation of acid secretion.

Histamine H2-receptor antagonists inhibit basal and all kinds of stimulated acid secretion with about the same effectiveness, and hence, local release of histamine is thought to be necessary for the stimulation of parietal cells. A local histamine pool is physiologically relevant only if it is within the diffusion distance of the parietal cells, if it is effectively mobilized by gastrin, and if it is endowed with the machinery for a rapid replenishment of the histamine that has been released. Histamine in the stomach occurs in endocrine cells (so-called enterochromaffin-like (ECL) cells), mast cells, and neurons. The ECL cells are peptide hormone-producing cells. In mammals they are located basally in the oxyntic gland area, in the chief-cell-rich region. Parietal cells predominate in t he mid-region. ECL cells respond readily to gastrin with histamine release and histamine resynthesis. Thus, the ECL cells fulfil important prerequisites of a physiologically relevant histamine pool. however, it is not apparent how the preferential localization of ECL cells at the base of the glands may be conducive to a direct effect of released histamine ont he parietal cells, unless histamine reaches the parietal cells via capillary transport from the glandular base. Mast cells are numerous int he stomach of, for example, man, pigs, dogs, and cats. They occur scattered throughout the stomach wall without any obvious relation to the parietal cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Trophic effects of gastrin.

Gastrin is an important trophic hormone for the acid-producing part of the stomach. There is no solid evidence that gastrin is physiologically important as a trophic agent outside the stomach. The trophic effects in the stomach are manifested as an increased weight and thickness of the oxyntic mucosa and can be induced by both exogenous and endogenous gastrin--that is, in situations of long-lasting hypergastrinemia (treatment with effective antisecretagogues, partial fundectomy, or antrum exclusion). Removal of endogenous gastrin by antrectomy induces the opposite effects--that is, diminished weight and thickness of the oxyntic mucosa. Unlike all other peptide hormone-producing endocrine cells in the oxyntic mucosa, the so-called enterochromaffin-like (ECL) cells respond readily to gastrin. An acute gastrin challenge results in release of stored products from the ECL cells (such as histamine) and activation of cytoplasmic enzymes (such as histidine decarboxylase). Sustained elevation of circulating gastrin over days results in hypertrophy of the ECL cells and over weeks results in marked hyperplasia (at most a fivefold increase in the rat). The results in other species are similar but often somewhat less marked than in the rat.

Animals↗
PubMed1991

The neuroendocrine system of the gut--an update.

During the last few years the endocrine stomach has come into focus much due to the side-effects produced by powerful acid blockers. A sustained and marked inhibition of acid secretion in the rat results in hypergastrinemia, with gastrin cell hyperplasia, and a consequent hyperplasia of the ECL cells. This response of the ECL cells was predictable in view of previous observations that sustained hypergastrinemia causes ECL cell hyperplasia. While the gastrin cell hyperplasia levels off at about twice the normal cell density a few weeks after start of treatment, the ECL cells continue to proliferate for months to reach a five-fold higher density than normally. Evidence is accumulating that ECL cells proliferate through self replication. After life-long inhibition of acid production (high doses of ranitidine or omeprazole) or after extirpation of 75% of the acid-producing part of the stomach, ECL cell carcinoids develop. Endocrine cells in the gut often contain more than one putative messenger. Thus, gastrin cells in many species store GABA and peptide YY; in e.g. cat and man they store in addition a xenopsin-like peptide. Neuromedin U and pituitary adenylate cyclase activating peptide (PACAP) have recently been demonstrated in gut nerves. Their role in gut physiology remains to be identified.

Animals↗
PubMed1991

GLP-1 and GLP-1(7-36) amide: influences on basal and stimulated insulin and glucagon secretion in the mouse.

We studied the cellular distribution of glucagon-like peptide-1 (GLP-1) in the pancreas and gut and the effects of GLP-1 and its truncated form, GLP-1(7-36) amide, on basal and stimulated insulin and glucagon secretion in the mouse. Immunofluorescence staining showed that GLP-1 immunoreactivity occurred within peripheral islet cells and in cells located mainly distally in the small intestine and in the entire large intestine. Double-immunostaining revealed that the GLP-1-immunoreactive cells were identical to the glucagon/glicentin cells. Experiments in vivo revealed that basal insulin secretion was stimulated by GLP-1(7-36) amide at the dose levels of 8 and 32 nmol/kg, and by GLP-1 at 32 nmol/kg. Furthermore, GLP-1(7-36) amide showed additive stimulatory influence with glucose (2.8 mmol/kg), the cholinergic agonist carbachol (0.16 mumol/kg), and the C-terminal octapeptide of cholecystokinin (CCK-8, 5.3 nmol/kg), when injected at 8 or 32 nmol/kg. In contrast, stimulated insulin secretion was unaffected by GLP-1. Moreover, the glucagon secretory responses to carbachol and CCK-8 were inhibited by GLP-1(7-36) amide but were unaffected by the entire GLP-1. We conclude that GLP-1(7-36) has the potential for being a modulator of islet hormone secretion.

Animals↗